Clinical Trials Resource Center

Cancer Treatment

July 11, 2016

Bayer reported results of a phase III trial of Stivarga (regorafenib) for patients with unresectable hepatocellular carcinoma (HCC) who progressed after treatment with Nexavar (sorafenib) tablets. The RESORCE trial was a randomized, double blind, placebo controlled, multicenter study enrolling 573 patients randomized in a 2:1 ratio to receive either regorafenib plus best supportive care (BSC) or placebo plus BSC. Patients received 160mg regorafenib once daily, for three weeks on/one week off, or placebo. Median progression-free survival was 3.1 months in patients taking regorafenib v. 1.5 months in the control group (HR 0.46; 95% CI 0.370.56; p<0.001). Median time to progression was 3.2 v. 1.5 months (HR 0.44; 95% CI 0.360.55; p<0.001). Disease control rate (composed of complete or partial response and stable disease) was 65.2% v. 36.1%, respectively (p<0.001). Overall response rates (complete and partial response) were 10.6% v. 4.1% (p=0.005), respectively. Bayer plans to submit data from the RESORCE study as the basis for marketing authorization of regorafenib in the treatment of unresectable HCC in the U.S. and other markets worldwide in 2016.

July 4, 2016

Celator Pharmaceuticals issued results of a phase III trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (CPX-351) in patients with high-risk acute myeloid leukemia (AML). The randomized, controlled trial enrolled 309 patients, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients. Patients were randomized 1:1 to receive either VYXEOS or 7+3. First induction for VYXEOS was 100u/m2; days one, three and five by 90-minute infusion, and for the control arm was cytarabine 100mg/m2/day by continuous infusion for seven days and daunorubicin 60mg/m2 on days one, two and three (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days one and three, and the control arm was cytarabine 100mg/ m2/day by continuous infusion for five days and daunorubicin 60mg/m2 on days one and two (5+2). An improvement in overall survival was also observed in FLT3 mutated patients with median overall survival of 10.25 months in the VYXEOS arm compared to 4.55 months in the 7+3 arm. The Hazard Ratio (HR) was 0.57 (p=0.093). In addition, preliminary data on NPM1 and CEBP mutations were presented showing an improvement in response rate and overall survival in patients with these mutations. The company expects to submit a NDA for VYXEOS with the FDA by the end of the third quarter of 2016.

June 13, 2016

Array BioPharma released results of a phase II trial of encorafenib for BRAF-mutant colorectal cancer. In the phase II trial, 102 patients were randomized 1:1 to receive encorafenib and cetuximab with or without alpelisib. Median PFS was 5.4 months and 4.2 months for the triplet and doublet regimens, respectively. An early analysis of median OS exceeded one year for the triplet regimen and was not reached for the doublet regimen. Confirmed ORR was 27% (95% CI, 16-41%) for the triplet regimen and 22% (95% CI, 12-36%) for the doublet regimen. Grade 3/4 AEs occurring in greater than 10% of patients in either arm included anemia, hyperglycemia and increased lipase. Historical published PFS and OS results after first-line treatment range between 1.8 to 2.5 months and four to six months, respectively, and published response rates from various studies in this population range between 6% to 8%.

Genmab reported results of a phase III POLLUX study (MMY3003) of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The study enrolled 569 patients who had relapsed or refractory multiple myeloma. The trial met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR)=0.37 (95% CI 0.27-0.52), p<0.0001). Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended that the data be unblinded. Patients originally assigned to the lenalidomide plus dexamethasone alone treatment group will be offered the option of receiving daratumumab monotherapy following confirmed disease progression.

June 6, 2016

Array BioPharma released results of a phase III trial of binimetinib for NRAS-mutant melanoma. In the trial, 402 patients with NRAS-mutant melanoma were randomized 2:1 to receive binimetinib or dacarbazine, respectively. The primary endpoint of PFS was met, with a hazard ratio of 0.62, [95% CI 0.47-0.80] and a p-value of less than 0.001. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm. Importantly, an improvement in median PFS in binimetinib-treated patients was observed in the pre-specified sub-group of patients who received prior treatment with immunotherapy. The median PFS on the binimetinib arm was 5.5 months versus 1.6 months on the dacarbazine arm [HR=0.46 (95% CI 0.26-0.81)]. Confirmed overall response rate and disease control rate were 15% (95% CI, 11-20%) and 58% (95% CI, 52-64%) for all patients receiving binimetinib, respectively, versus 7% (95% CI, 3-13%) and 25% (95% CI, 18-33%) for patients receiving dacarbazine, respectively. Grade 3/4 adverse events reported in greater than or equal to 5% of patients receiving binimetinib included increased creatine phosphokinase and hypertension. The company plans to submit an NDA in the next month.

May 16, 2016

SELLAS Life Sciences Group issued results of a phase II trial of WT1 (Galinpepimut-S) cancer vaccine in patients with malignant pleural mesothelioma (MPM). The randomized, double-blind, placebo-controlled trial compared the WT1 analog peptides vaccine in combination with Montanide-adjuvant + Granulocyte-macrophage colony-stimulating factor (GM-CSF) versus Montanide-adjuvant + GM-CSF in patients with MPM who had previously completed combined modality therapy. Thirty-nine patients were to be enrolled in each arm at two centers. The trial showed a median overall survival of 21.4 months for WT1 vaccine-treated patients versus a median 16.6 months overall survival for patients in the placebo control arm. The WT1 cancer vaccine also resulted in a median progression-free survival of 11.4 months, double that of the control arm, 5.7 months, in patients with MPM. The WT1 vaccine demonstrated a favorable safety and tolerability profile in MPM patients. Patients with a complete tumor resection and subsequent treatment with WT1 showed a significant survival benefit. Patients who mounted an immune-response with WT1 had a significant survival benefit. WT1 was very well-tolerated by patients in this trial. Based on these results, SELLAS is preparing to initiate a pivotal phase IIb/III trial of its WT1 vaccine in patients with MPM by the third quarter of 2016.

April 25, 2016

Morphotek reported results of a phase III trial of farletuzumab (MORAb-003) in combination with a platinum standard chemotherapy regimen (carboplatin plus taxane) in platinum-sensitive ovarian cancer patients in first relapse. All subjects received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomized test product 1:1:1 farletuzumab 1.25mg/kg, farletuzumab 2.5mg/kg, or placebo), and single-agent test product was continued weekly until disease progression. Neither farletuzumab dose met the study’s primary progression-free survival (PFS) endpoint when compared to placebo, with PFS of 9.0, 9.5 (hazard ratio [HR]=0.99) and 9.7 months (HR=0.86) for the placebo, farletuzumab 1.25mg/kg, and farletuzumab 2.5mg/kg arms, respectively. There was no difference in overall survival. Prespecified subgroup analyses demonstrated that subjects with a low CA125 level (less than three times the upper limit of normal) correlated with longer PFS (HR=0.49) and OS (HR=0.44) for farletuzumab 2.5mg/kg versus placebo. Subjects with higher farletuzumab exposure also showed superior PFS and OS compared to placebo. The most common adverse events were those known to be associated with chemotherapy, including alopecia, nausea, neutropenia, fatigue, thrombocytopenia and neuropathy. Morphotek has initiated a phase II trial to investigate the potential clinical benefit observed in patients with a low CA125 level.

April 11, 2016

BioLineRx issued results from BL-8040’s phase II trial in relapsed or refractory acute myeloid leukemia (r/r AML). The trial was a multicenter, open-label study assessing pharmacodynamics and pharmacokinetic parameters of BL-8040 in combination with Cytarabine (Ara-C). Forty-two patients with r/r AML were enrolled in the study (36 of which received a dose of 1mg/kg and higher). The study included a dose escalation stage followed by an expansion stage. Each patient received a once daily dose of BL-8040 monotherapy (from 0.5 to 2mg/kg) on days one to two, followed by the same dose of BL-8040 plus Ara-C on days three to seven. Extensive pharmacodynamic parameters, such as mobilization of leukemic cells and induction of apoptosis, were assessed after monotherapy with BL-8040 using peripheral blood sampling and bone marrow aspirates at baseline and on day three prior to Ara-C administration. Clinical response to treatment was evaluated by bone marrow biopsy on day 30. Results showed BL-8040, as a single agent and in combination with Cytarabine (Ara-C), was safe and well-tolerated at all doses tested up to and including the highest dose level of 2mg/kg, with no major adverse events (n=45). The composite complete remission rate, including both complete remission (CR) and complete remission with incomplete blood count recovery (CRi), was 38% in subjects receiving up to two cycles of BL-8040 treatment at doses of 1mg/kg and higher (n=39). The company plans multiple additional clinical studies for BL-8040. An AML consolidation treatment is currently being investigated in a large phase IIb study at in Germany.  

March 28, 2016

Janssen-Cilag International issued phase III results of ZYTIGA (abiraterone acetate) plus prednisone for early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). COU-AA-302 was an international, randomized, double-blind, placebo-controlled study that included 1,088 men with mCRPC who had not received prior chemotherapy and were randomized to receive ZYTIGA (abiraterone acetate) 1,000 milligrams (mg) administered orally once-daily plus prednisone 5mg administered twice-daily or placebo plus prednisone 5mg administered twice-daily. The co-primary endpoints of the study were rPFS and OS. The post-hoc analysis used the final dataset for the intent-to-treat population (n=1,088), to stratify patients into Group 1 (BPI 0-1, PSA <80 ng/ml and GS <8) and Group 2 (BPI=2 and/or PSA=80ng/ml and/or GS=8). The study provided an 11.8 months overall survival (OS) benefit (53.6 months vs. 41.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055), compared to an active control of placebo plus prednisone. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostate-specific antigen [PSA] below 80ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with ZYTIGA plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR=0.61 [95% CI, 0.43-0.87]; p=0.0055) (Group 2: 2.8 months; HR=0.84 [95% CI, 0.72-0.99]; p=0.0321).

March 21, 2016

Biofrontera issued results of its phase III clinical trial evaluating BF-200 ALA for the treatment of basal cell carcinoma (BCC). Results of the EU-based, multicenter study confirm that 93.4% of patients treated with BF-200 ALA were cleared of all BCCs, compared to only 91.8% of patients treated with the comparator treatment, methyl aminolaevulinate (MAL) photodynamic therapy, which is marketed as Metvix or Metvixia. In the study, 281 patients with one to three non-aggressive BCCs, including both superficial and nodular BCC subgroups, up to a thickness of 2mm were treated. The analysis of the individual BCCs yielded a complete clearance rate of 94.6% after treatment with BF-200 ALA, compared to 92.9% with MAL (all values refer to the per protocol group). A stronger deviation of efficacy between the two drugs became apparent in thicker tumors. While 96.4% of tumors between 0 and 1mm thickness were completely removed by treatment with BF-200 ALA (95.7% MAL), the value decreased in 1 to 2mm tumors to 72.7% with BF-200 ALA and 66.7% with MAL. 89.3% of nodular BCCs, a subgroup of non-aggressive BCCs, were completely cleared with BF-200 ALA in comparison to only 78.6% with MAL. In addition, treatment with BF-200 ALA resulted in an excellent cosmetic outcome. In 60% of patients treated with BF-200 ALA, skin aesthetic appearance was strongly improved and rated by study physicians as very good to excellent, compared to only 48.6 % of patients treated with MAL. To evaluate these characteristics, various skin parameters had been qualified by the study physicians and graded by the severity of skin damage. The improvement of each parameter was documented and included in the analysis. An unsatisfactory result without cosmetic improvement was observed in 17.1% of BF-200 ALA patients and 18.9% of patients treated with MAL.

February 16, 2016

Leap Therapeutics released results of a four part (Part A, Part B, Part C and Part D), dose-escalating, open label, multicenter study evaluating the safety, pharmacokinetics and efficacy of DKN-01 in combination with paclitaxel in adult patients with recurrent or metastatic esophageal or gastro-esophageal junction cancer with progressive disease requiring therapy. Nine patients with cancer of the esophagus or GEJ were enrolled in the Part A dose escalation; all were evaluable per the protocol. Patients received either 150mg or 300mg twice monthly in combination with weekly infusions of 80mg/m2 paclitaxel. The combination of DKN-01 and paclitaxel was safe and well-tolerated at all doses. There were no treatment related severe adverse events (SAEs), or treatment emergent adverse events (TEAE) leading to study discontinuation. Three patients had PRs and four patients had best responses of Stable Disease, with a total disease control rate of 77.7%. Treatment with 300mg of DKN-01 twice monthly was selected for further study in combination with weekly infusions of 80mg/m2 paclitaxel. Patients with adenocarcinoma of the esophagus or GEJ with fewer lines of therapy may derive greater benefit (n=4, ORR=75%, median PFS=37.3 weeks).

February 8, 2016

OncoGenex Pharmaceuticals reported results of a phase II trial evaluating the combination of apatorsen with carboplatin and pemetrexed in patients with untreated metastatic non-small cell lung cancer (NSCLC). Data did not reach the statistical significance required to demonstrate a progression-free survival (PFS) benefit. The placebo-controlled, double-blind, randomized trial enrolled 155 subjects. A potential PFS benefit was observed in patients with high baseline serum Hsp27 status when treated with apatorsen. The study is ongoing and overall survival results are expected in the second half of 2016. Treatment and maintenance therapy with apatorsen was well-tolerated. Adverse events were comparable between the arms and as expected for the study chemotherapy treatment.  

February 1, 2016

Leap Therapeutics, a biotechnology company developing novel therapeutics at the leading edge of cancer research, reported its first results of a clinical trial of its lead candidate DKN-01, a monoclonal antibody against the Dickkopf-1 (DKK1) protein. Data from the trial demonstrated meaningful clinical activity in relapsed or refractory cancer of the esophagus or gastro-esophageal junction (GEJ), indications with limited approved therapies. In Part A of the study, the dose escalation phase, three of nine patients achieved a partial response (PR) per RECIST v1.1. In the subset of patients with adenocarcinoma who had received one or two prior lines of therapy, three of four patients achieved a PR. “Patients with relapsed or refractory esophageal carcinoma have an extremely poor prognosis,” commented David Ryan, M.D. Massachusetts General Hospital. “The results from the study of DKN-01 in combination with paclitaxel, while early, provide great encouragement, and we look forward to the data from the next phases of this trial.”

January 25, 2016

Merrimack Pharmaceuticals issued results of a phase III study of ONIVYDE (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin achieved a substantial improvement in 12-month overall survival in patients with post-gemcitabine metastatic pancreatic adenocarcinoma when compared to 5-FU and leucovorin alone. The randomized, open label study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy was the largest phase III study in this setting to date. A total of 417 patients were randomized across the three arms. Primary survival analysis was based on 313 events and showed that ONIVYDE in combination with 5-FU and leucovorin significantly improved overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio (HR) =0.67, 95% CI: [0.49-0.92]). The monotherapy regimen in this study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.77-1.28]). No new safety or tolerability concerns were note in the updated analysis. The primary NAPOLI-1 study results were the basis of the recent FDA and Taiwan FDA approval of ONIVYDE in combination with 5-FU and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Merrimack and Baxalta have entered into an exclusive licensing agreement for the development and commercialization of ONIVYDE outside of the U.S. and Taiwan. Baxalta’s marketing authorization application for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy is currently under review with the EMA.

Novocure issued results of a phase II trial showing Tumor Treating Fields (TTFields) therapy plus first-line chemotherapy gemcitabine is tolerable and safe in patients with advanced pancreatic cancer. The first cohort of the prospective, single-arm study included 20 patients with advanced pancreatic cancer whose tumors could not be removed surgically and who had not received chemotherapy or radiation therapy prior to the clinical trial. The primary endpoint measured the incidence and severity of treatment-related adverse events. As a result of TTFields therapy, 10 patients experienced treatable contact dermatitis. No serious adverse events related to TTFields were reported. Fourteen patients reported serious adverse events unrelated to TTFields therapy. In relation to these reported results for gemcitabine alone, PANOVA patients who received TTFields therapy plus first-line gemcitabine experienced a median progression free survival of 8.3 months compared to 3.7 months, a median overall survival of 14.9 months compared to 6.7 months and a median one-year survival of 55% compared to 22%. Thirty percent of the evaluable tumors had partial responses compared to 7% with gemcitabine alone and another 30% had stable disease. The PANOVA trial includes a second cohort testing TTFields plus gemcitabine and nab-paclitaxel in an additional 20 patients. Based on these data, the company will accelerate planning of a phase III clinical trial in pancreatic cancer. 

Sellas Life Sciences Group reported positive results from a phase I/II clinical study of the WT1 cancer vaccine in patients with multiple myeloma (MM) following autologous stem cell transplantation. Sellas’s trial enrolled 15 patients, each patient receiving chemotherapy and stem cell transplantation and followed by one to two cycles (six vaccines per cycle) of the company’s WT1 cancer vaccine. Of the patients enrolled, 60% were found to have high risk cytogenetics at diagnosis (9/15), including del p53; this is the most difficult population to maintain in long-lasting remission. Initial data have shown positive safety findings and that treatment with the WT1 vaccine was well-tolerated. Initial results from the study have demonstrated positive immune response data and safety findings as well as early efficacy data. Three patients with high-risk cytogenetics achieved an immune response against WT1 peptides encoded in the vaccine, and two of these patients continued in remission at the time of last follow-up at one year; the third patient was in remission as of the first, three-month follow-up and will continue to be followed through one year. Sellas intends to assess the efficacy of the WT1 cancer vaccine in MM in a larger phase II/III trial including patients with standard risk disease following induction chemotherapy in 2016.

January 18, 2016

Astellas US and Medivation released results from the phase II TERRAIN trial of enzalutamide compared to bicalutamide in metastatic castration-resistant prostate cancer (CRPC). The trial enrolled 375 patients in North America and Europe, and evaluated enzalutamide 160mg once daily versus bicalutamide 50mg once daily. The TERRAIN study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared to bicalutamide (hazard ratio=0.44; 95% confidence interval, 0.34-0.57; p<0.0001). Median PFS, defined as time from randomization to centrally confirmed radiographic progression, skeletal-related event, initiation of new anti-neoplastic therapy or death, whichever occurred first, was 15.7 months in the enzalutamide group compared to 5.8 months in the bicalutamide group. The observed adverse event profile of enzalutamide in TERRAIN appeared consistent with that from phase III enzalutamide trials. The median time on treatment in TERRAIN was 11.7 months in the enzalutamide group versus 5.8 months in the bicalutamide group. Serious adverse events were reported in 31.1% of enzalutamide-treated patients and 23% of bicalutamide-treated patients. Individual grade three or higher adverse events largely occurred at a similar rate (<1% difference) between treatment groups, with the exception of hypertension (7.1% v. 4.2%) and back pain (2.7% v. 1.6%), which occurred more frequently in the enzalutamide treatment group. Grade three or higher cardiac events were reported in 5.5% of enzalutamide-treated patients versus 2.1% of bicalutamide-treated patients. Two seizures were reported in the enzalutamide group and one in the bicalutamide group.

Genentech reported results of a phase II study of venetoclax for chronic lymphocytic leukemia (CLL). The study met its primary endpoint, with an overall response rate (ORR) of 79.4% with venetoclax, as assessed by an independent review committee (IRC). In addition, 7.5% of people achieved a complete response with or without complete recovery (complete response without normal blood counts) in the bone marrow. Forty-five people had an assessment for minimal residual disease (MRD) in the blood. Notably 18 people (17% of the total, 21% of responders) achieved MRD-negativity, meaning no cancer could be detected using a specific test. Ten of these 18 people also had bone marrow assessments and six were MRD-negative. At one year, 84.7% of all responses and 94.4% of MRD-negative responses were maintained. The one-year progression-free survival (PFS) and overall survival (OS) rates were 72% and 86.7%, respectively. No unexpected safety signals were reported. AbbVie has submitted an NDA for venetoclax to the FDA. Venetoclax received Breakthrough Therapy designation from the FDA earlier this year for the treatment of people with relapsed or refractory CLL harboring the 17p deletion. AbbVie also has submitted a marketing authorization application (MAA) to the EMA. Submissions to other regulatory authorities around the world are planned in 2016.

Sorrento Therapeutics reported results of a phase III study of STI-001 in China for epidermal growth factor receptor (EGFR) expressing metastatic colorectal carcinoma patients. STI-001 was used in combination with irinotecan versus irinotecan alone. The combination therapy showed significant improvement compared to chemotherapy alone in overall response rate (ORR: 32.9% v. 12.8%) and progress-free survival (PFS: 5.6 v. 3.2 months) as well as longer overall survival (OS: 14.1 v. 13.4 months). The ORR, PFS and OS using STI-001 and irinotecan are increased significantly than previously reported in similar medical settings using Erbitux and irinotecan (32.9% v. 10%; 5.6 v. 4 months; 14.1 v. 11.6 months). During the 501-patient, double-blind, randomized trial, STI-001 was well-tolerated. Adverse events (AEs), especially grade three and four AEs, were found to be significantly fewer than those previously reported using Erbitux. While it was reported that more than 10% of patients using Erbitux showed hypersensitive reaction (grade three/ four), none was recorded in the completed phase III study of STI-001.

January 11, 2016

Exelixis has issued results of a phase III trial comparing cabozantinib to everolimus in 658 patients with renal cell carcinoma (RCC). The trial met its primary endpoint of demonstrating a statistically significant increase in PFS for cabozantinib as compared to everolimus, as determined by an independent radiology committee. Per the trial protocol, the primary analysis was conducted among the first 375 patients randomized to ensure sufficient follow-up and a PFS profile that would not be primarily weighted toward early events. The median PFS for that population was 7.4 months for the cabozantinib arm v. 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (hazard ratio [HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001). As assessed by an independent radiology committee, the median PFS across all enrolled patients was 7.4 months for the cabozantinib arm v. 3.9 months for the everolimus arm, corresponding to a 48% reduction in the rate of disease progression or death for cabozantinib as compared to everolimus (HR = 0.52, 95% CI 0.43-0.64, p<0.001). Cabozantinib currently is marketed in capsule form under the brand name Cometriq in the U.S. for the treatment of progressive, metastatic medullary thyroid cancer (MTC), and in the E.U. for the treatment of adult patients with progressive, unresectable locally advanced or metastatic MTC.

December 21, 2015

Spectrum Pharmaceuticals has reported results of a phase I combination trial of belinostat (Beleodaq) with the CHOP (cyclophosphamide, hydroxyl-doxorubicin, Oncovin and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Oncovin is a brand name for vincristine. The open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the expansion phase, enrolled 12 additional patients at that dose level. The MTD of belinostat was established at 1,000mg/m2 IV infusion on days one through five (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: complete response + partial response) and pharmacokinetics. Results showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a complete response (14/21), and 19% achieving a partial response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) grade three/four hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No grade three/four non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study. Beleodaq is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the FDA for the treatment of relapsed or refractory PTCL in July 2014.

December 14, 2015

Takeda Pharmaceutical has reported results of a phase III trial of NINLARO (ixazomib) for relapsed and/or refractory multiple myeloma. The TOURMALINE-MM1 trial is an international, randomized, double-blind, placebo-controlled trial designed to evaluate once-weekly oral ixazomib plus lenalidomide and dexamethasone compared to placebo plus lenalidomide and dexamethasone. Trial results demonstrate a statistically significant (35%) improvement in progression free survival (PFS), with patients treated in the ixazomib arm living for a significantly longer time without their disease worsening compared to patients in the control arm (20.6 months vs. 14.7 months in control group; Hazard Ratio [HR] 0.742; p = 0.012). Overall response rate (ORR) was 78.3% in the ixazomib arm and median duration of response was 20.5 months, v. 71.5% and 15 months in the control group. Median PFS in high-risk patients (HR 0.543; HR 0.596 in patients with del(17p)) was similar to that in the overall patient population and in standard-risk patients. The most common grade three adverse events included neutropenia, anemia, thrombocytopenia and pneumonia. Gastrointestinal events included diarrhea, nausea, and vomiting. Peripheral neuropathy rates were 28% in the IRd arm v. 21% in the control arm, 35% v. 21% had rash events, 8% v. 10% had acute renal failure, and 4% v. 3% had heart failure. NINLARO was recently approved by the FDA in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

December 7, 2015

Exelixis has issued results of a phase III trial of Cotellic (cobimetinib) in patients with previously untreated resectable, locally advanced or metastatic melanoma carrying a BRAF V600E or V600K mutation, in combination with vemurafenib. In October, Exelixis announced the coBRIM trial met its OS secondary endpoint, demonstrating a statistically significant increase in OS for the combination of Cotellic and vemurafenib compared to vemurafenib monotherapy. The median OS was 22.3 months for the combination of Cotellic and vemurafenib v. 17.4 months for vemurafenib alone, corresponding to a 30% reduction in the rate of death for the combination as compared to vemurafenib alone (hazard ratio [HR]=0.70, 95% confidence interval [CI] 0.55-0.90, p=0.005). Ongoing study monitoring did not identify any new safety signals. On Nov. 10, the FDA approved Cotellic as a treatment for patients with BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma, in combination with vemurafenib. Cotellic was first approved in Switzerland in late August. The Cotellic approvals are based on data from coBRIM, the phase III pivotal trial conducted by Genentech in 495 patients with previously untreated unresectable, locally advanced or metastatic melanoma carrying a BRAF V600 mutation. Genentech sponsored the U.S. NDA and Roche sponsored the Swiss regulatory application. Roche also filed a Marketing Authorization Application (MAA) with the EMA in late 2014, and the Committee for Medicinal Products for Human Use issued a positive recommendation on the MAA in September of this year. Roche anticipates a decision from the European Commission by year-end.

Merrimack and Baxalta have reported results of a global, randomized, open-label phase III trial of Onivyde, in combination with 5-FU and leucovorin, for treatment of metastatic adenocarcinoma of the pancreas. Patients were enrolled at 76 sites in North America, South America, Europe, Asia and Oceania. A total of 417 patients were randomized across the three arms. The Onivyde combination regimen demonstrated a significant increase in median overall survival v. 5-FU and leucovorin alone: 6.1 months v. 4.2 months (p=0.012, unstratified hazard ratio for death (HR) =0.67, 95% CI: [0.490.92]). The monotherapy regimen in the study did not show improvement over the 5-FU and leucovorin arm: 4.9 v. 4.2 months (p=0.94, HR=0.99, 95% CI: [0.771.28]). Onivyde in combination with 5-FU and leucovorin achieved a longer progression- free survival compared with the 5-FU and leucovorin arm (3.1 months v. 1.5 months; unstratified HR=0.56 [95% CI, 0.410.75]). Unconfirmed objective response rate was higher in the Onivyde in combination with 5-FU and leucovorin arm than in the 5-FU and leucovorin arm: 16% (19/117) v. 1% (1/119) (difference 15.4 percentage points, 95% CI, 8.5-22.3; p<0.0001). The most common grade three or four adverse events that occurred more frequently in the Onivyde combination arm (>2% incidence v. 5-FU and leucovorin) were neutropenia, diarrhea, vomiting and fatigue. Study results were the basis of the recent FDA and Taiwan FDA approval. In May 2015, the EMA accepted for review Baxalta’s marketing authorization application for Onivyde based on the same clinical results.

November 16, 2015

Merck has reported results of a randomized, pivotal phase II/III study comparing two doses of Keytruda (the FDA-approved 2mg/kg dose and a higher, investigational 10mg/kg dose, each given every three weeks) to docetaxel, a commonly used chemotherapy, for advanced non-small-cell lung cancer (NSCLC). KEYNOTE-010 is a global, open-label study in 1,034 patients. A topline analysis revealed that treatment with Keytruda was associated with longer overall survival (OS) compared with docetaxel treatment. That result was true for both the approved and the investigational dose of Keytruda, which showed similar efficacy. It was also true in both the first set of patients analyzed—those with a tumor proportion scores (TPS) of 50% or greater and for all enrolled patients, all of whom had a TPS of 1% or greater. Treatment with Keytruda, at both doses, also provided superior progression-free survival (PFS) v. that achieved following treatment with docetaxel in patients whose tumors had TPS values equal to or greater than 50%. For PFS, Keytruda treatment was numerically but not statistically superior to docetaxel in the all PD-L1 positive group, again at both doses. The safety profile of Keytruda in that trial was consistent with that observed in previously reported studies in patients with advanced NSCLC.

November 2, 2015

Immunomedics has reported results of a phase III trial of sacituzumab govitecan for metastatic triple-negative breast (TNBC), small-cell (SCLC) and non-small-cell lung (NSCLC) cancers. At the time of analysis, 56 enrolled patients had received sacituzumab govitecan at the optimal dose of 10mg/kg given on days one and eight of a three-week cycle. Treatment response was available for 52 patients. The objective response rate was 29% (15/52), with two confirmed complete responses. The interim median progression-free survival (PFS), a measure of time patients are living without their cancer progressing, was seven months. Forty-six percent of these TNBC patients had experienced a PFS event. Overall survival (OS) data were too early to report because 86% of patients are still alive. For metastatic lung cancers, 33 patients with NSCLC were enrolled to receive sacituzumab govitecan at the 8.mg/kg or 10mg/kg dose level. Among 29 patients assessable, an objective response rate of 28% (8/29) was observed, including patients with both squamous cell and adenocarcinoma NSCLC types. For the 25 patients at the 10mg/kg dose, the interim median PFS was 3.8 months, with 48% of patients in this dose group having experienced a PFS event. In SCLC, of the 27 patients enrolled at doses of 8mg/kg and 10mg/kg, 25 were assessable for response. Six patients achieved a partial response (objective response rate=24%). Interim median PFS for the 12 patients at the 10mg/kg dose level was 3.6 months and 83% of patients had experienced a PFS event. Since 96% of NSCLC patients and 100% of SCLC patients were still alive at the time of analysis, OS data at the optimal dose of 10mg/kg are too early to report. Sacituzumab govitecan has received Fast Track designation from the FDA for the treatment of patients with TNBC, SCLC and NSCLC, and also has been designated an orphan drug for SCLC or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the E.U.

October 26, 2015

BeyondSpring Pharmaceuticals has released results of a phase III study of Plinabulin combined with docetaxel for non-small cell lung cancer (NSCLC) in patients who have lung lesions greater than 3cm. Patients were randomized one-to-one in a Plinabulin plus docetaxel treatment arm compared to docetaxel alone. Patients in the treatment arm received 30mg/m2 dose of Plinabulin, which was selected as the dose for an ongoing phase III study. Analysis of median overall survival (OS) according to tumor size of any lesion demonstrated evident OS benefit in favor of Plinabulin and docetaxel treatment arm, as shown by hazard ratio (HR). In patients with lesions greater than 3 cm, HR gradually decreased to <0.6. The HR range was 0.97-0.50. That trend was consistently observed independent of number of prior treatments. The importance of location of lesions also was analyzed. It was apparent that patients with advanced lesions in lung parenchyma received more benefit from Plinabulin plus docetaxel treatment (HR=0.76) regardless of lesion size. The HR range (0.84-0.44) based on lung lesion size also was consistent with findings based on size of all lesion including extra-pulmonary lesions. Treatment with Plinabulin plus docetaxel was well-tolerated, with most common adverse events consistent with chemotherapy side effects and including nausea, fatigue, diarrhea, constipation, anorexia, fever, vomiting and transient blood pressure elevation, which were mostly grade 1-2.

October 19, 2015

OncoSec Medical has issued results of a phase II trial of ImmunoPulse IL-12 for merkel cell carcinoma (MCC). OMS-I110 was an open-label study that enrolled 15 patients with MCC. In the study, 79% of patients (11/14) showed an increase in IL-12 protein levels in tumor biopsy samples obtained about 22 days after treatment compared to baseline, indicating that ImmunoPulse IL-12 leads to successful DNA transfection and sustained protein expression within the tumor microenvironment. ImmunoPulse IL-12 was well-tolerated, with no treatment-related adverse events above grade two and no treatment-related serious adverse events. The most common adverse event was grade one transient pain associated with the treatment procedure. Analysis of individual lesions found that 30% of patients (3/10) who were evaluable for systemic anti-tumor immunity had regression of at least one distant, non-injected/ non-electroporated lesion. In patients considered evaluable for objective response by modified RECIST criteria (i.e., cohort B, N=12), 25% of patients (3/12) had an objective partial response (PR) and one patient had stable disease (SD) for a disease control rate (PR + SD) of 33%. In cohort A (N=3), one patient had a pathologic complete response and continues to be recurrence-free at six months. Another patient has been recurrence-free for over three years.

October 5, 2015

Boehringer Ingelheim has released results of a phase III trial of fatinib compared to erlotinib for the treatment of patients with previously treated advanced squamous cell carcinomas (SCC) of the lung. More patients had improved overall health-related quality-of-life (36% v. 28%, p=0·041), cough (43% v. 35%, p=0·029) and dyspnoea (51% v. 44%, p=0·061) with afatinib than with erlotinib. The rate of severe adverse events in the LUX-Lung 8 trial was similar between the two treatment arms with differences observed in the incidence of certain side effects. A higher incidence of severe diarrhoea and stomatitis (mouth sores) was observed with afatinib compared to erlotinib (grade 3 diarrhoea: 10% v. 2%; grade 3 stomatitis: 4% v. 0%), while a higher incidence of severe rash/acne was reported with erlotinib compared to afatinib (grade 3 rash/acne: 10% v. 6%). Diarrhoea occurring in patients treated with afatinib was manageable. Afatinib is under review by both the FDA and EMA for the treatment of SCC of the lung. Afatinib also has been granted Orphan Drug designation by the FDA. Afatinib currently is approved in more than 60 countries for the first-line treatment of specific types of EGFR mutation-positive non-small cell lung cancer.

Exelixis has issued results of a phase III trial comparing cabozantinib to everolimus in 658 patients with renal cell carcinoma who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor. The median PFS was 7.4 months for the cabozantinib arm v. 3.8 months for the everolimus arm, corresponding to a 42% reduction in the rate of disease progression or death for cabozantinib as compared to the everolimus arm (hazard ratio [HR]=0.58, 95% confidence interval [CI] 0.45-0.75, p<0.001). The company is on track to complete an NDA filing with the FDA by the end of 2015. Cabozantinib has received Breakthrough Therapy designation in the U.S. and Exelixis expects a European filing to follow in early 2016.

September 8, 2015

Janssen R&D has released results from a multicenter, two-part, open-label, phase I/II study of daratumumab for relapsed or refractory multiple myeloma. In part 1, 32 patients were treated with escalating doses and no maximum tolerated dose was identified. In part 2, 72 patients were enrolled in a dose expansion cohort and received either 8mg/kg (30 patients) or 16mg/kg (42 patients) of daratumumab at various schedules until disease progression or unmanageable toxicity to optimize doses identified in part 1. Following that study, 16 mg/kg was chosen as the dose to be used in all daratumumab clinical trials. Patients had a median of four prior lines of therapy and 79% were refractory to their last therapy, including both lenalidomide and bortezomib (64%). Additionally, 76% of patients previously received an autologous stem cell transplant. In the 16mg/kg cohort, the ORR was 36% (11 partial responses, two very good partial responses and two complete responses) and 10% in the 8mg/kg cohort (three partial responses). The two complete responses were confirmed with the use of a novel assay. Median progression-free survival was 5.6 months (95% CI: 4.2, 8.1) and 65% (95% CI: 28, 86) of responders remained in remission at 12 months. In the 16mg/kg cohort, serious adverse events (AEs) occurred in 33% of patients. Infusion-related reactions (IRRs) occurred in 71% of patients in both the 8mg/kg and 16mg/kg cohorts, and all were grades 1 and 2, except for the occurrence of grade 3 reactions in one patient. The majority of IRRs occurred during the first infusion, with notably fewer during subsequent infusions. No patient discontinued treatment due to an IRR. The most common AEs in either treatment group were fatigue, allergic rhinitis and pyrexia (fever). On July 9, Janssen completed the rolling submission of its BLA for daratumumab to the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an IMiD, or who are double refractory to a proteasome inhibitor and an immunomodulatory agent. Daratumumab received Breakthrough Therapy designation from the FDA for this patient population in May 2013.

August 10, 2015

Lexicon Pharmaceuticals reported results of a phase III study of telotristat etiprate for carcinoid syndrome patients with metastatic neuroendocrine tumors (NET). The double-blind study enrolled 135 patients and evaluated two doses of oral telotristat etiprate— 250mg and 500mg, each taken three times daily—against placebo over a 12-week period. Top-line results show that patients who added telotristat etiprate to SSA therapy at both the 250mg and 500mg doses experienced a statistically significant reduction from baseline compared to placebo in the average number of daily bowel movements over the 12-week study period (p<0.001), meeting the study’s primary endpoint. In another key finding, a substantially greater proportion of patients on telotristat etiprate achieved a durable response (44% and 42% in the 250mg and 500mg arms, respectively), defined as at least a 30% reduction in daily bowel movements over at least half the days of the study period, as compared to 20% response on placebo (p<0.040). The 12-week double-blind study period is being followed by a 36-week open-label extension where all patients receive telotristat etiprate 500mg three times daily.

July 13, 2015

Novartis issued results of a phase III study of with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) compared to Tafinlar monotherapy alone for BRAF V600E/K mutation-positive metastatic melanoma. COMBI-d is a pivotal, phase III, randomized, double-blinded study in patients with unresectable (stage IIIC) or metastatic (stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The study randomized 423 patients. The final OS analysis showed that the combination of Tafinlar and Mekinist achieved a statistically significant OS benefit compared to Tafinlar monotherapy (median of 25.1 months v. 18.7 months; Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI), 0.55-0.92], p=0.011). A 33% reduction in the risk of progression or death was demonstrated with the combination therapy compared to monotherapy (median PFS of 11 months in the 211 patients receiving combination therapy v. 8.8 months in the 212 patients receiving monotherapy; HR 0.67 [95% CI, 0.53-0.84], p<0.001). The combination achieved ORR of 69% compared to 53% for monotherapy [difference=15% (95% CI, 6.0%-24.5%), p=0.001]. The median DoR for the 144 responders receiving combination therapy was 12.9 months [95% CI, 9.4-19.5] compared to 10.6 months in the 113 responders receiving monotherapy [95% CI, 9.1-13.8]. The safety results were consistent with the profile observed to date for the combination and consistent with the profile observed for Tafinlar monotherapy; no new safety concerns were observed. Completion of COMBI-d is a post-marketing requirement for the FDA’s accelerated approval for the combination in the U.S.

June 29, 2015

Genentech released results of a phase II study of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) and docetaxel chemotherapy for HER2-positive early breast cancer (eBC). The randomized, multicenter, international study enrolled 417 people with newly diagnosed HER2-positive, operable, locally advanced or inflammatory eBC. Participants were randomized to one of four study arms and received four cycles (12 weeks) of neoadjuvant treatment followed by surgery and a year of adjuvant treatment with Herceptin plus chemotherapy. Both progression-free survival (PFS) and disease-free survival (DFS) were evaluated at three years. The results suggested that people who received the Perjeta regimen prior to surgery were 31% less likely to experience disease worsening, recurrence or death (PFS HR=0.69; 95% CI, 0.34–1.40) compared to those who received Herceptin and chemotherapy. People treated with the Perjeta regimen also were 40% less likely to experience disease recurrence or death (DFS HR=0.60; 95% CI, 0.28–1.27). The results suggested that people who achieved pathological complete response (pCR; no tumor tissue detectable at the time of surgery in the affected breast and local lymph nodes) were more likely across all arms of the study to be alive and disease-free at three years (PFS HR=0.54; 95% CI, 0.29–1.00; DFS HR=0.68; 95% CI, 0.36–1.26). It previously was reported that the Perjeta regimen significantly increased the number of people who achieved pCR compared to Herceptin and docetaxel chemotherapy (39.3% v. 21.5%). In 2013, the FDA granted accelerated approval of the Perjeta regimen for neoadjuvant treatment in people with high-risk, HER2-positive eBC. Roche recently submitted a MAA to the EMA for the Perjeta regimen as a neoadjuvant treatment for people with HER2-positive eBC.

June 22, 2015

OncoGenex Pharmaceuticals released results of a phase III study of custirsen therapy in men with metastatic castrate-resistant prostate cancer (CRPC) who had a poor prognosis. The trial evaluated custirsen plus docetaxel/prednisone compared with docetaxel/prednisone alone in men with metastatic CRPC (n=1,022). Following 509 deaths, median overall survival (OS) was 23.4 months (m) v. 22.2 m for custirsen and control arms, respectively (hazard ratio [HR] 0.93; P = 0.42). Median survival for the poor and good prognosis groups in the control arm was 14 m and 30.4 m, respectively (HR = 3.66). The custirsen HR effect differed between poor and good prognosis groups (interaction P = 0.069). The HR estimate for custirsen survival benefit for those in the poor prognosis group was 0.73 (95% CI: 0.59 to 0.90) and 1.02 (95% CI: 0.76 to 1.37) for those in the good prognosis. When analyzed separately (n=492), the median OS in the poor prognostic group was 17 m in the custirsen arm v. 14 m in the control arm (HR=0.73, 95% CI: 0.59 to 0.90, P = 0.004).

June 15, 2015

Janssen R&D reported results of a phase III study of trabectedin (Yondelis) compared to dacarbazine for advanced liposarcoma (LPS) or leiomyosarcoma (LMS) previously treated with an anthracycline and at least one additional chemotherapy regimen. Both treatments were administered via an IV infusion every three weeks with the trabectedin dose of 1.5mg/m2 given over 24 hours v. dacarbazine dose of 1g/m2 given over 20-120 minutes. In this randomized, active-controlled study in patients with advanced LPS or LMS, trabectedin significantly reduced the risk of disease progression or death by 45% compared with those who received dacarbazine (hazard ratio [HR] = 0.550; P<0.0001; median [M] 4.2 v. 1.5 months, respectively), with results validated through an audit by independent radiologists. Safety findings were consistent with the well-characterized safety profiles of both agents, with the most common grade 3-4 toxicities in the trabectedin v. the dacarbazine groups being decreased absolute neutrophil count (40% v. 25%), decreased platelets (19% v. 20%) and transient increases in liver transaminases, including alanine transaminase (29% v. 1%). Drug-related deaths occurred in 2.1% of patients in the trabectedin group v. 0% of patients in the dacarbazine group. Trabectedin is approved in 77 countries in North America, Europe, South America and Asia for the treatment of advanced STS as a single agent. Janssen submitted an NDA to the FDA on November 24, 2014, which was granted Priority Review on February 3, 2015.

March 30, 2015

Astellas Pharma and Medivation issued results from a phase II study of enzalutamide compared to bicalutamide in metastatic castration-resistant prostate cancer (CRPC). The phase II trial enrolled 375 patients in North America and Europe and was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. bicalutamide at a dose of 50mg taken once daily. The median PFS in the enzalutamide arm was 9.9 months longer compared to that in the bicalutamide arm (15.7 v. 5.8 months, respectively) with a Hazard Ratio (HR) of 0.44 (95% confidence interval [CI], 0.34-0.57; p<0.0001). The median time to PSA progression was 13.6 months longer with enzalutamide (19.4 months) relative to bicalutamide treatment (5.8 months) with an HR of 0.28 (p<0.0001). 82% of enzalutamide-treated patients achieved >= 50% PSA reduction from baseline by week 13 v. 21% of bicalutamide-treated patients. The median time on enzalutamide treatment was 11.7 months compared to 5.8 months on bicalutamide.

March 2, 2015

Immunomedics reported results of a study of sacituzumab govitecan for treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A total of 44 heavily-pretreated patients with relapsed or refractory lung cancer have been enrolled into this multicenter study. At the time of analysis, 16 patients with SCLC and 18 with NSCLC were evaluated by computed tomography for response and time-to-progression (TTP). Despite the late-stage setting, TTP for most patients was longer with sacituzumab govitecan than the duration of their previous lung cancer therapy. 33% of patients with SCLC and 31% with NSCLC had their tumor reduced in size by 30% or more. Sacituzumab govitecan controlled the progression of the cancer in 75% and 56% of NSCLC and SCLC patients, respectively. These patients had either failed to respond to their last lung cancer therapies or their cancer had returned or progressed. Sacituzumab govitecan continues to produce an acceptable safety profile in heavily-pretreated patients, with neutropenia (24% grades three and four combined) as the major toxicity. Diarrhea, the typical side effect of irinotecan treatment, was minimal at 3% grade three. More importantly, repeated efficacious doses of the ADC can be given to patients over months without evoking any interfering immune response.

February 16, 2015

GlaxoSmithKline released results of a phase III comparison study of the BRAF inhibitor, dabrafenib, and the MEK inhibitor, trametinib, to single-agent therapy with dabrafenib and placebo in patients with unresectable (stage IIIC) or metastatic (stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The pivotal, phase III, randomized, double-blinded study enrolled 423 patients from investigative sites in Australia, Europe and North and South America. Overall survival results demonstrate a statistically significant reduction in the risk of death (Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI): 0.55, 0.92], p=0.011) for the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) compared to dabrafenib monotherapy in patients with BRAF V600E/K mutation-positive metastatic melanoma. The safety profile was consistent with the profile observed to date for the combination; no new safety concerns were observed. At the time of the primary analysis, the most common adverse events (=20%) for the combination arm were pyrexia, fatigue, headache, nausea, chills, joint pain (athralgia), diarrhoea, rash, hypertension and vomiting. More patients had AEs leading to dose modifications with combination arm compared to dabrafenib monotherapy. Increased incidence (51% v. 28%) and severity (grade 3, 6% v. 2%) of pyrexia occurred with combination. Increased incidence of hyperkeratosis (32% v. 3%) occurred with dabrafenib monotherapy. Completion of this study is a post-marketing requirement for the FDA’s Accelerated Approval for the combination in the U.S. The final data from COMBI-d will be submitted in the coming months.

February 9, 2015

Boehringer Ingelheim released results of two phase III trials of afatinib compared to standard chemotherapy for epidermal growth factor receptor (EGFR) mutation-positive patients with metastatic non-small cell lung cancer (NSCLC). In the two individual phase III studies, treatment-naïve patients with stage IIIB/IV lung adenocarcinoma and confirmed EGFR mutations in the tumor were enrolled in LUX-Lung 3 (n=345; recruited globally) and LUX-Lung 6 (n=364; recruited in China, Korea and Thailand). Patients were randomized (2:1) to receive oral afatinib (40mg/day) or up to six cycles of intravenous pemetrexed/cisplatin (LUXLung 3) or gemcitabine/cisplatin (LUX-Lung 6) at standard doses. Stratification factors included EGFR mutation type (Del19 v. L858R v. other “uncommon” mutations) and race (Asian v. non-Asian; LUX-Lung 3 only). Results from both trials showed similar OS in the afatinib and chemotherapy arms in the overall NSCLC EGFR mutation-positive population (LUX-Lung 3: median OS 28.2 to 28.2 months, HR 0.88; p=0.39); (LUX-Lung 6: median OS 23.1 to 23.5 months, HR 0.93; p=0.61). There was a survival benefit of more than a year (LUX-Lung 3: median OS 33.3 to 21.1 months; HR 0.54; p=0.0015); (LUX-Lung 6: median OS 31.4 to 18.4 months; HR 0.64; p=0.0229).

CytRx reported results of a phase IIb study of aldoxorubicin compared with doxorubicin as first-line therapy in subjects with metastatic, locally advanced or unresectable soft tissue sarcomas (STS). In this randomized, open-label, 123-subject, 31-center, phase IIb trial, subjects with advanced soft tissue sarcomas were randomized 2:1 to receive either 350mg/m2 of aldoxorubicin (83 subjects) or 75mg/m2 of doxorubicin (40 subjects) every three weeks for up to six cycles. Subjects were then followed every six weeks with CT scans to monitor tumor size. The OS results in 123 patients showed aldoxorubicin-treated patients demonstrated a 27% reduction in the risk of death compared to patients treated with doxorubicin (HR 0.73: 95% confidence interval 0.44-1.20), the current standard-of-care in this indication. In addition, aldoxorubicin-treated patients demonstrated a 41% likelihood of surviving more than two years, a two-fold increase, compared to a 20% probability for doxorubicin- treated patients. Median overall survival was 16 months (95% confidence interval 13.1-not reached) for aldoxorubicin-treated patients v. 14.4 months (95% confidence interval 8.7-20.9) for doxorubicin-treated patients (p=0.21). For treatment-naive patients, representing 90% of the patients in the clinical trial, median overall survival was 16 months (95% confidence interval 13.1-not reached) for aldoxorubicin-treated patients v. 14 months (95% confidence interval 8.7-20.1) for doxorubicin treated patients (p=0.14). Progression-free survival (PFS) results demonstrated treatment with aldoxorubicin increased median PFS approximately 79% to 8.4 months, compared to 4.7 months with doxorubicin, meeting the study’s primary endpoint (HR=0.419; p=0.0007). In blinded central radiology review, PFS results demonstrated treatment with aldoxorubicin increased median PFS approximately 104% to 5.7 months, compared to 2.8 months with doxorubicin, also meeting the study’s primary endpoint (HR=0.584; p=0.024).

February 2, 2015

Medivation and Astellas Pharma reported results of a phase II study comparing enzalutamide with bicalutamide in men with metastatic castration-resistant prostate cancer. The phase II TERRAIN trial enrolled 375 patients in North America and Europe. The trial involved patients with metastatic prostate cancer whose disease progressed despite treatment with a luteinizing hormone-releasing hormone (LHRH) analogue therapy or following surgical castration. The trial was designed to evaluate enzalutamide at a dose of 160mg taken once daily v. bicalutamide at a dose of 50mg taken once daily, the approved dose in combination with an LHRH analogue. The study achieved its primary endpoint demonstrating a statistically significant increase in progression-free survival (PFS) for enzalutamide compared to bicalutamide (Hazard Ratio=0.44; 95% Confidence Interval, 0.34- 0.57; p<0.0001). Median PFS was 15.7 months in the enzalutamide group compared to 5.8 months in the bicalutamide group. The median time on treatment in TERRAIN was 11.7 months in the enzalutamide group v. 5.8 months in the bicalutamide group. Serious adverse events were reported in 31.1% of enzalutamide-treated patients and 23.3% of bicalutamide-treated patients. Grade 3 or higher cardiac adverse events were reported in 5.5% of enzalutamide-treated patients v. 2.1% of bicalutamide-treated patients. Two seizures were reported in the enzalutamide group and one in the bicalutamide group. The most common side effects occurring during treatment and more common in the enzalutamide- treated v. bicalutamide-treated patients included fatigue, hot flush, hypertension, diarrhea, weight decreased and pain in extremity.

PharmaEngine released results of a phase II study of PEP02 (MM-398, liposome irinotecan injection) in unresectable metastatic colorectal cancer (mCRC). The PEPCOL study evaluated the efficacy and safety of PEP02 (MM-398) in combination with 5-FU/LV (FUPEP regimen) or irinotecan plus 5-FU/LV (FOLFIRI regimens: FOLFIRI-1 or modified FOLFIRI-3) as a secondline therapy in patients with mCRC. The primary endpoint was the objective response rate (ORR). Fifty-five patients were randomized (FUPEP, n=28; FOLFIRI, n=27) and non-comparative randomly assigned to FUPEP (PEP02 80mg/m² d1, folinic acid (FA) 400mg/m² d1, 5-FU 2,400mg/m² d1-2) or FOLFIRI (FOLFIRI-1: irinotecan 180mg/ m² d1, FA 400mg/m² d1, 5-FU bolus 400mg/m² d1, 5-FU infusion 2,400mg/m² d1-2; or modified FOLFIRI-3: irinotecan 90mg/m² d1 and 3, FA 400mg/m² d1, 5-FU infusion 2,400mg/m² d1-2). Bevacizumab q2w (5mg/kg) was allowed in both arms as of June 2012. In the intent to treat population, the ORR of the FUPEP regimen was 14% (4/28), which compared favorably with FOLFIRI-1 (0%, 0/10) and was comparable to the modified FOLFIRI-3 regimen (18%, 3/17). Most common grade 3-4 adverse events reported in the respective FUPEP and the FOLFIRI arms were neutropenia (11% v. 30%) and diarrhea (21% v. 33%), which were numerically lower in the FUPEP arm than in the FOLFIRI arm; other aspects of the safety profiles were similar between the two arms. Based on the acceptable safety profile of the FUPEP regimen in this PEPCOL study, it was added as the third arm to the phase III metastatic pancreatic cancer (NAPOLI-1) study in which this FUPEP regimen (MM-398 + 5-FU/LV arm) met the primary endpoint of a statistically significant improvement in overall survival.

January 26, 2015

PharmaEngine released results of a phase III study of MM-398 (PEP02, liposome irinotecan injection) for metastatic pancreatic cancer. The global, randomized, openlabel study evaluated two MM-398 regimens, 80mg/m2 combined with 5-fluorouracil (5- FU) and leucovorin (LV) every two weeks, and 120mg/m2 as a monotherapy every three weeks. Each arm was compared to a control arm of 5-FU and LV. A total of 417 patients were randomized across the three arms. Each MM-398 regimen was compared against the control arm on the primary endpoint of overall survival. Patients were enrolled at 76 sites of the 105 sites initiated in North America, South America, Europe, Asia and Australia. The primary analysis demonstrated a statistically significant increase in overall survival with an unstratified hazard ratio of 0.67 (95% CI [0.49-0.92], p=0.0122) and a median of 6.1 months for the combination of MM-398 plus 5-FU/LV compared to 4.2 months in the 5-FU/LV control arm. In the stratified analysis, which accounts for pre-specified prognostic factors included in the study randomization stratification, the overall survival for MM-398 in combination with 5-FU/LV compared to control arm resulted in a hazard ratio of 0.57 (95% CI [0.41-0.80], p=0.0009). In the Per Protocol population (defined by patients who received 80% of protocol defined dose and were able to remain on treatment for at least six weeks), MM-398 in combination with 5-FU/LV demonstrated superior overall survival and tumor control to the control arm of 5-FU/LV alone. In the Per Protocol analysis, median overall survival for the combination therapy arm was 8.9 months versus 5.1 months in the control arm (stratified HR = 0.47, 95% CI [0.29-0.77], p=0.0018).

January 12, 2015

OncoGenex Pharmaceuticals reported results of a phase II study of apatorsen in combination with gemcitabine/cisplatin chemotherapy compared to chemotherapy alone in the treatment of metastatic bladder cancer. The trial, Borealis-1, enrolled approximately 180 patients with documented metastatic or locally inoperable transitional cell carcinoma (TCC) of the urinary tract who previously had not received chemotherapy for metastatic disease and were not candidates for potentially curative surgery or radiotherapy. Patients were randomized to receive standard chemotherapy (gemcitabine/cisplatin) in combination with apatorsen at two dose levels (600mg and 1,000mg) or gemcitabine/cisplatin plus placebo. Patients received up to six cycles of weekly intravenous therapy. Overall trial results indicated the addition of 600mg apatorsen to standard of care chemotherapy showed a 14% reduction in risk of death (overall survival hazard ratio (HR) = 0.86) and a 17% reduction in progressive disease and death (progression-free survival HR = 0.83) when compared to chemotherapy alone. Over one-third of the patients in the trial had lower performance status, as defined by a Karnofsky score of 80% or less. These patients derived the greatest benefit from 600mg apatorsen in combination with chemotherapy, resulting in a 50% reduction in risk of death (overall survival HR = 0.50) compared to chemotherapy alone. Less benefit was observed in the 1000mg apatorsen arm due to increased adverse events leading to a higher rate of discontinuation of both apatorsen and chemotherapy. Apatorsen 600mg was well tolerated in combination with chemotherapy.

December 1, 2014

GlaxoSmithKline reported results of a phase III study of trametinib (Mekinist) and dabrafenib (Tafinlar) compared to vemurafenib monotherapy in previously untreated patients with BRAF V600E/K mutation- positive metastatic melanoma. This phase III, randomized (1:1), open-label study enrolled 704 patients globally. The study demonstrated a 31% decrease in the risk of death for patients treated with the trametinib and dabrafenib combination compared to vemurafenib (Hazard Ratio [HR] 0.69; 95% Confidence Interval [CI] 0.53, 0.89; two-sided P=0.005). Median OS for the vemurafenib arm was 17.2 months; median OS for the combination arm had not been reached. At 12 months, the rate of OS was 72% for the combination arm and 65% for the vemurafenib arm. Treatment with the combination increased median progressionfree survival to 11.4 months compared to 7.3 months for the vemurafenib arm. Overall, treatment with the combination resulted in a 44% reduction in risk of disease progression or death (HR, 0.56; 95% CI 0.46, 0.69; two-sided P-value <0.001) compared to vemurafenib. The objective response rate was 64% (95% CI 59.1%, 69.4%) for the combination and 51% (95% CI 46.1%, 56.8%) for vemurafenib (P<0.001); the median duration of response was 13.8 months (95% CI 11.0, not reached) v. 7.5 months (95% CI 7.3, 9.3), respectively. Additionally, 13% of patients treated with the combination achieved a complete response, compared to 8% of patients in the vemurafenib arm.

November 10, 2014

Bristol-Myers Squibb reported results from a phase II, single-arm, open-label study of Opdivo (nivolumab) in patients with advanced squamous cell non-small cell lung cancer (NSCLC) who have progressed after at least two prior systemic treatments with 65% receiving three or more prior therapies (n=117). The trial, Checkmate -063, was designed to assess advanced squamous cell NSCLC patients who progressed after both platinum-based therapy and at least one additional systemic therapy, with an ECOG Performance Status of zero or one. Subjects were treated with Opdivo as a single agent 3mg/kg by intravenous infusion every two weeks until disease progression or treatment discontinuation (n=117). With approximately 11 months of minimum follow up, the objective response rate (ORR, the study’s primary endpoint) was 15% (95% CI = 8.7, 22.2) as assessed by an independent review committee (IRC) using RECIST 1.1 criteria, and the median duration of response was not reached. The estimated one-year survival rate was 41% (95% CI = 31.6, 49.7) and median overall survival (mOS) was 8.2 months (95% CI = 6.05, 10.91). Grade 3-4 drug-related adverse events (AEs) were reported in 17.1% of patients. The most common Grade 3-4 AEs (greater than or equal to 2%) were fatigue (4.3%), pneumonitis (3.4%) and diarrhea (2.6%). Discontinuations due to drug-related AEs of any grade occurred in 12% of patients, and there were two drug-related deaths in patients with multiple co-morbidities and in the setting of progressive disease.

October 20, 2014

Boehringer Ingelheim issued results of a phase III trial of afatinib v. erlotinib in patients with advanced squamous cell carcinoma (SCC) of the lung. In the randomized, open-label trial, 795 patients with stage IIIB/IV SCC of the lung were randomized 1:1 to receive afatinib or erlotinib until disease progression. The planned primary analysis was based on 414 progression-free survival (PFS) events by independent review in the first 669 patients randomized (afatinib: 335, erlotinib: 334) while recruitment was ongoing. Afatinib significantly reduced the risk of disease progression by 18% when compared to erlotinib and delayed tumor growth (PFS by independent review: 2.4 v. 1.9 months; HR=0.82; p=0.043). Treatment with afatinib showed improvement in the secondary endpoint of disease control rate (DCR) compared to erlotinib (DCR: 45.7% v. 36.8%; p=0.020). Objective response rate was 4.8% in the afatinib arm v. 3% in the erlotinib arm (p=0.233). More patients reported an improvement in their global health status/quality of life (p=0.026) and cough (p=0.01) with afatinib v. erlotinib; no difference was observed with pain (p=1.0) and dyspnea (p=0.298) between groups. There was no significant difference in the time to deterioration across these four measures. The overall rate of severe (>/= grade 3) adverse events was comparable between both therapies. Incidence of severe adverse events was 50.2% in patients treated with afatinib compared to 49.1% with erlotinib. A higher incidence of severe diarrhea and stomatitis was observed in patients treated with afatinib compared to erlotinib (severe diarrhea: 9% v. 2%; stomatitis: 3% v. 0%), while there was a higher incidence of severe rash/acne observed with erlotinib compared to afatinib (9% v. 6%).

Puma Biotechnology issued results of a phase II trial of PB272 (neratinib) for the treatment of non-small cell lung cancer (NSCLC) with HER2 mutations. In the trial, patients with confirmed stage IIIB or stage IV NSCLC with documented somatic HER2 mutations were randomized to receive either oral neratinib monotherapy, 240mg per day, or the combination of oral neratinib, 240mg daily, with intravenous temsirolimus administered at a dose of 8mg per week. A total of 27 patients completed the first stage of the trial; 13 of these patients received neratinib monotherapy and 14 of these patients received the combination of neratinib plus temsirolimus. Results showed that of the 13 patients who received neratinib monotherapy, no patient experienced a partial response, seven (54%) patients achieved stable disease and four (31%) patients achieved clinical benefit (defined as a partial response or stable disease for 12 or more weeks). For the 14 patients who received the combination of neratinib plus temsirolimus, three (21%) patients experienced a partial response, 11 (79%) patients experienced stable disease and nine (64%) patients achieved clinical benefit. The median progression free survival of the neratinib monotherapy arm was 2.9 months and the median progression free survival of the arm that received neratinib plus temsirolimus was four months. Patients continue to be enrolled in the arm of the trial that is receiving the combination of neratinib plus temsirolimus.

October 13, 2014

Janssen R&D issued results of a phase III study of ZYTIGA (abiraterone acetate) plus prednisone in men with chemotherapynaive metastatic castration-resistant prostate cancer (mCRPC). The international, randomized, double-blind, placebo-controlled study included 1,088 men with mCRPC who had not received prior chemotherapy and were randomized to receive ZYTIGA (abiraterone acetate) 1,000mg administered orally once daily plus prednisone 5mg twice daily or placebo plus prednisone 5mg twice daily. The study demonstrated a 19% reduction in risk of death in this study population (median OS, 34.7 v. 30.3 months, respectively; HR= 0.81 [95% CI, 0.70-0.93]; p = 0.0033), after a median follow-up of more than four years (49.2 months). 67% of men in the ZYTIGA plus prednisone arm and 80% in the control arm received subsequent therapy. This includes 44% of men in the control arm who subsequently received ZYTIGA plus prednisone. The use of subsequent therapies did not impact the statistical significance between the ZYTIGA and control arms and makes these results all the more compelling after adjusting for the crossover effect. Final analysis demonstrated a significant improvement in median time to opiate use for cancer-related pain compared to placebo plus prednisone (median 33.4 v. 23.4 months, respectively; HR= 0.72 [95% CI, 0.61-0.85]; p = 0.0001). With two additional years (a total of four years) of follow-up since the last clinical cutoff (median 49.2 months), the safety profile of ZYTIGA remained unchanged compared to previous reports. Janssen has initiated regulatory submissions to health authorities for a revision to the ZYTIGA label.

October 6, 2014

Bristol-Myers Squibb released results of a phase III trial of Opdivo (nivolumab) v. investigator’s choice chemotherapy (ICC) in patients with advanced melanoma who were previously treated with Yervoy (ipilimumab). In the randomized, controlled, open-label study (n=370), patients were randomized 2:1 to receive Opdivo 3mg/kg by intravenous infusion every two weeks (n=268) or ICC (dacarbazine 1000mg/m2 every three weeks or carboplatin [AUC] 6 plus paclitaxel 175mg/ m2 every three weeks; n=102) until progression or unacceptable toxicity. The objective response rate (ORR) was 32% (95% CI = 24, 41) in the Opdivo arm and 11% (95% CI = 4, 23) in the ICC reference arm in patients with at least six months of follow up. The majority of Opdivo treatment-related adverse events (AEs) were grade 1/2 and managed using recommended treatment algorithms. Grade 3/4 drug-related AEs were less frequent for the Opdivo arm (9% versus 31% of patients treated chemotherapy). Serious Grade 3/4 drug-related AEs were reported in 5% and 9% of patients treated with Opdivo and ICC, respectively. Discontinuations due to drug-related AEs, of any grade, occurred in 2% of Opdivo-treated patients and 8% of patients administered ICC.

Genentech reported results of a phase III trial of cobimetinib in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma harboring a BRAF V600 mutation. The trial was an international, randomized, double-blind, placebo-controlled study evaluating 60mg once daily of cobimetinib in combination with 960mg twice daily of vemurafenib, compared to 960mg twice daily of vemurafenib alone. In the study, 495 patients with BRAF V600 mutation-positive unresectable locally advanced or metastatic melanoma, and previously untreated for advanced disease, were randomized to receive vemurafenib every day on a 28-day cycle plus either cobimetinib or placebo for days 1-21. Median follow up was 7.4 months for the combination arm and 7.2 months for the control arm. The median PFS was 9.9 months for the combination of cobimetinib and vemurafenib v. 6.2 months for vemurafenib alone (hazard ratio [HR]=0.51, 95% CI 0.39-0.68; p<0.0001), demonstrating the combination reduced the risk of the disease worsening by half (49%). The median PFS by independent review committee (IRC), a secondary endpoint, was 11.3 months for the combination arm compared to six months for the control arm (HR=0.60, 95% CI 0.45-0.79; p=0.0003). Objective response rate (ORR) was 68% for the combination v. 45% for vemurafenib alone (p<0.0001). Overall survival data are not yet mature (HR=0.65, 95% CI 0.42-1.00; p=0.046). Roche has submitted an MAA to the EMA, and Genentech plans to submit an NDA to the FDA later this year.

August 25, 2014

Austrianova released results of a phase II study of Cell-in-a-Box combined with ifosfamide for treatment of advanced, inoperable cancer. Thirteen patients with advanced, inoperable pancreatic cancer have been treated with the Cell-in-a-Box/ifosfamide combination in the uncontrolled (no comparator arms), open-label study. A single implantation of Cell-in-Box capsules (each capsule contained approximately 10,000 cells capable of converting the anticancer prodrug ifosfamide into its “cancer-killing” form by virtue of their overexpression of an isoform [CYP2B1] of human cytochrome P450) was used and two courses of treatment with ifosfamide were administered. There were no deleterious effects, such as inflammation or pancreatitis, that could be attributed to the Cell-in-a-Box capsules being implanted in the patients. The median survival of patients in the phase I/II clinical trial was about 40 weeks versus the 33 weeks seen in the phase II clinical trial. The percentage of patients who survived one year was somewhat lower in the phase II clinical trial (23%) than in the phase I/II clinical trial (38%). The dose (1g/ m2) of ifosfamide used in the phase I/II clinical trial was one-third of the “normal” dose of ifosfamide, whereas the dose used in the phase II clinical trial was twice (2g/m2) that dose. A phase IIb trial has been planned in Australia implementing the 1g/m2 dose of ifosfamide instead of the 2g/m2 dose.

August 11, 2014

Amgen and Onyx Pharmaceuticals reported results of a phase III study of Kyprolis (carfilzomib) for injection in combination with Revlimid (lenalidomide) and low-dose dexamethasone (KRd) for multiple myeloma. Patients were randomized to receive Kyprolis (20mg/m on days one and two of cycle one only, then 27mg/m subsequently), in addition to a standard dosing schedule of lenalidomide (25mg per day for 21 days on, seven days off) and low-dose dexamethasone (40mg per week in four week cycles), versus lenalidomide and low-dose dexamethasone alone. The study randomized 792 patients at sites in North America, Europe and Israel. Patients treated with Kyprolis for injection in combination with Revlimid and low-dose dexamethasone lived significantly longer without their disease worsening (median 26.3 months) compared to patients treated with Revlimid and low-dose dexamethasone (Rd) (median 17.6 months) (HR=0.690, 95% CI, 0.570, 0.834, p<0.0001). Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. These results will form the basis for regulatory submissions throughout the world beginning in the first half of 2015.

August 4, 2014

Celsion released result of an ongoing, open-label phase II trial of ThermoDox in recurrent chest wall breast cancer (RCWBC). The trial is designed to enroll 20 patients at several U.S. clinical sites and is evaluating ThermoDox in combination with mild hyperthermia. Of the 13 patients enrolled and treated, 10 were eligible for evaluation of efficacy. To date, 60% of patients experienced a stabilization of their highly refractory disease with a local response rate of 50% observed in the 10 evaluable patients, notably three complete responses, two partial responses and one patient with stable disease.

July 14, 2014

Taiho Oncology issued results of a phase III trial of TAS-102 (trifluridine and tipiracil hydrochloride) for the treatment of refractory metastatic colorectal cancer. The trial was a global, randomized, double-blind, placebo-controlled comparison trial. The trial enrolled 800 patients in North America, Japan, Europe and Australia who received at least two prior regimens of standard chemotherapies for mCRC and were refractory to, or failed, those chemotherapies. Patients were randomized (2:1) to receive TAS-102 (35mg/m2) or placebo, plus best supportive care, twice daily. The trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (H =0.68, p<0.0001). TAS-102 reduced the risk of mortality by 32% when compared to placebo. Median overall survival was 7.1 months (95% CI: 6.5-7.8) and 5.3 months (95% CI: 4.6-6.0) for TAS-102 and placebo, respectively, and was improved in favor of TAS-102 by 1.8 months. There also was a statistically significant 52% decrease in the risk of disease progression between the two arms (HR=0.48, p<0.0001). In addition, the disease control rate of patients treated with TAS-102 was 44.0% versus 16.3% for patients treated with placebo (p<0.0001). Taiho plans to submit regulatory submissions in the U.S. at the end of 2014 and in Europe in the first quarter of 2015.

June 23, 2014

Novartis reported phase I trial results of Zykadia (LDK378) in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). The 246 patients with ALK+ NSCLC in this single-arm study received ceritinib 750mg ALK+ daily. Findings from the study showed patients treated with ceritinib achieved an ORR of 58.5% [95% CI, 52.1-64.8%] and a median PFS of 8.2 months [95% CI, 6.7-10.1 months]. The median duration of response was 9.7 months [95% CI, 7.0-11.4 months], with a median time to first response of six weeks after starting treatment. Among 163 patients receiving 750 mg of ceritinib daily and who were previously treated with the commonly prescribed ALK inhibitor crizotinib, ORR was 54.6% [95% CI, 46.6-62.4%] and PFS was 6.9 months [95% CI, 5.4-8.4 months]. In 83 patients who had not received prior treatment with an ALK inhibitor, ORR was 66.3% [95% CI, 55.1-76.3%] and PFS had not been reached. In the 124 patients who started the study with brain metastases, ceritinib achieved an ORR of 54.0% [95% CI, 44.9-63.0%] and a median PFS of 6.9 months [95% CI, 5.4-8.4 months]. Tumor shrinkage was seen in 50.0% of patients [49 of 98 patients; 95% CI, 39.7-60.3%] with brain metastases who had received previous ALK inhibitor therapy, while 69.2% of patients [18 of 26 patients; 95% CI, 48.2-85.7%] with brain metastases who were not previously treated achieved tumor shrinkage following treatment with ceritinib.

June 2, 2014

Boehringer Ingelheim reported result of two phase III trials (LUX-Lung 3 and LUX-Lung 6) of afatinib for treatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. The LUX-Lung 3 trial compared afatinib with chemotherapy (pemetrexed/cisplatin); LUX-Lung 6 evaluated afatinib v. chemotherapy (gemcitabine/cisplatin) for Asian patients. Afatinib prolonged survival of lung cancer patients whose tumors have common EGFR mutations compared with standard chemotherapy by a median of three months (27.3 to 24.3 months) and significantly reduced the risk of death by 19% (HR=0.81, p=0.037). The most pronounced reduction in risk of death was 41% (HR=0.59, CI 0.45, 0.77) in patients whose tumors have the most common EGFR mutation (exon 19 deletion of the EGFR gene); for patients with the exon 21 (L8585R) mutation there was no impact on overall survival (HR=1.25, CI 0.92, 1.71). Those patients who continued afatinib treatment, with the addition of chemotherapy, after progressing on afatinib alone, had a further delay in tumor growth compared to the group who stopped afatinib treatment and received chemotherapy only (tumor growth was delayed by 5.6 months and 2.8 months respectively, p=0.003). This corresponded to a 40% reduction in risk of disease progression (HR=0.60). The most common adverse events in patients treated with afatinib and chemotherapy versus chemotherapy were diarrhea (53.8% v. 6.7%), hair loss or alopecia (32.6% v. 15%) and weakness or asthenia (27.3% v. 28.3%).

April 28, 2014

GlaxoSmithKline and Genmab released results of a phase III study of Arzerra (ofatumumab), in combination with chlorambucil for previously untreated patients with chronic lymphocytic leukemia (CLL). Results from the randomized, open-label, parallel-arm, pivotal phase III study evaluating the combination of ofatumumab and chlorambucil (N=221) v. chlorambucil alone (N=226) demonstrated statistically significant improvement in median PFS in patients randomized to ofatumumab and chlorambucil compared to patients randomized to chlorambucil alone (22.4 months v. 13.1 months, respectively) (HR=0.57 [95% CI, 0.45, 0.72] <0.001). The majority of adverse reactions (ARs) were Grade 2 or lower in both treatment arms. The most common (>/=5% in the ofatumumab plus chlorambucil arm and also >/=2% more than in the chlorambucil monotherapy arm) non-infusion-related ARs (all grades) as reported by investigators within 60 days following the last treatment were neutropaenia (27% ofatumumab + chlorambucil, 18% chlorambucil), asthaenia (8%, 5%), headache (7%, 3%), leukopaenia (6%, 2%), herpes simplex (6%, 4%), lower respiratory tract infection (5%, 3%), arthralgia (5%, 3%) and upper abdominal pain (5%, 3%).

April 14, 2014

Synta Pharmaceuticals issued interim results from a single-arm, multi-center, phase II proof-of-concept study designed to evaluate ganetespib for the treatment of metastatic breast cancer. Target enrollment is 35 patients in three cohorts, which include HER2+ breast cancer, triple-negative breast cancer (TNBC) and, recently added and now recruiting, ER/PR-positive patients previously untreated for locally advanced or metastatic disease. The goal of the trial design is to obtain initial evidence of a clinical activity signal with single-agent ganetespib administered for up to 12 weeks. Ten patients were enrolled into the HER2+ cohort and 38 patients were enrolled into the TNBC cohort. Of the patients evaluable for metabolic response based on having reached the week 3 PET assessment, six of seven achieved a metabolic response in the HER2+ cohort and 18 of 31 achieved a metabolic response in the TNBC cohort. Of the 6 HER2+ and 26 TNBC patients that reached the six-week assessment and therefore evaluable for objective RECIST response, four achieved an objective response and two achieved stable disease in the HER2+ cohort, while two achieved an objective response, 11 achieved stable disease and 13 had progressive disease in the TNBC cohort. One HER2+ patient achieved a complete objective response and has remained on treatment for over 10 months.

April 7, 2014

Novartis released results of a phase I study of LDK378 in 130 patients for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC). Of 114 ALK+ NSCLC patients treated with LDK378 at 400mg or higher per day, 80 had progressed during or following treatment with crizotinib, and 34 patients with ALK+ NSCLC were crizotinib-naive. The maximum tolerated dose observed in the study was 750mg per day. The median duration of response for the 66 responding patients treated at 400mg or higher per day was 8.2 months [95% CI; 6.9-11.4 months]. In all, 114 ALK+ NSCLC patients treated at 400mg or higher per day, median progression-free survival was 7 months [95% CI; 5.6-9.5 months]. In the 114 ALK+ NSCLC patients treated with LDK378 at 400mg or higher per day, the overall response rate (ORR) was 58% [95% CI; 48-67%] (1 complete response [CR] and 65 partial responses [PR]), which includes those patients who had progressed during or after crizotinib therapy (ORR 56% [95% CI; 45-67%]) and those who were crizotinibnaive (ORR 62% [95% CI; 44-78%]). In the 78 patients with ALK+ NSCLC who received LDK378 at the maximum tolerated dose of 750mg per day, the ORR was 59% [95% CI; 47-70%] (46 PRs), which includes those who had progressed during or after crizotinib therapy (ORR 56% [95% CI; 41-70%]) and those who were crizotinib-naive (ORR 64% [95% CI; 44-81%]). The most frequent adverse events were nausea (82%), diarrhea (75%), vomiting (65%), fatigue (47%) and increased alanine aminotransferase levels (35%). At the 750mg dose level, 50 of 81 patients (62%) required at least one dose reduction, of which 32 occurred in cycle three or later. The FDA has accepted regulatory filings for LDK378.

March 24, 2014

Amgen issued results of a phase III study of talimogene laherparepvec in patients with injectable unresected stage IIIB, IIIC or IV melanoma compared to granulocyte-macrophage colony-stimulating factor (GM-CSF). Of the 295 patients treated with talimogene laherparepvec, almost 4,000 tumor lesions were tracked. Half of these lesions were injected with talimogene laherparepvec at least once, while the rest were not injected, including visceral tumor lesions. The results showed a 50% or greater reduction in tumor size in 64% of injected tumors. In addition, one-third of uninjected non-visceral tumors, and 15% of visceral tumors, also were reduced by at least 50%. There were 35 melanoma-related surgeries performed during this trial, of which 30% successfully removed all residual disease. The most frequently observed adverse events in the phase III study were fatigue, chills and pyrexia. The most common serious adverse events include disease progression in both groups, and cellulitis and pyrexia in the talimogene laherparepvec group.

March 3, 2014

Eli Lilly reported results of a phase III study of ramucirumab in combination with chemotherapy in patients with second-line non-small cell lung cancer (NSCLC). The global, randomized, double-blind trial compared ramucirumab and docetaxel to placebo and docetaxel in NSCLC patients whose disease has progressed after failure of prior platinum-based chemotherapy for locally advanced or metastatic disease. Ramucirumab showed a statistically significant improvement in overall survival in the ramucirumab-plus-docetaxel arm compared to the control arm of placebo plus docetaxel, and a statistically significant improvement in progression-free survival in the ramucirumab arm compared to the control arm. The most common (>5% incidence) Grade 3 adverse events on the ramucirumab-plus-docetaxel arm were decreased white blood cell count (neutropenia/leukopenia), febrile neutropenia, fatigue/asthenia and hypertension.

February 17, 2014

Aeterna Zentaris reported results of a phase II trial of zoptarelin doxorubicin (AEZS-108) for the treatment of endometrial cancer. Forty-four patients entered into the study at eight centers in Germany and three centers in Bulgaria. Forty-three of these patients were eligible. Two patients had a complete remission (5%) and eight achieved a partial remission (18%). Stable disease for at least six weeks was observed in 44%. The median time to progression (TTP) was seven months and median overall survival (OS) was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%). Data showed zoptarelin doxorubicin has clinically meaningful activity with low toxicity in women with advanced or recurrent LHRH receptor positive endometrial cancer, supporting the principle of receptor mediated targeted chemotherapy. These results were the basis of a phase III trial of zoptarelin doxorubicin, currently enrolling.

Eisai reported positive results of a phase III trial of lenvatinib for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The study was a multicenter, randomized, double-blind, placebo-controlled, phase III study to compare the PFS of patients with radioiodinerefractory differentiated thyroid cancer and radiographic evidence of disease progression within the prior 12 months, treated with once-daily, oral lenvatinib (24mg) v. placebo. Secondary endpoints of the study included overall response rate (ORR), overall survival (OS) and safety. The study enrolled 392 patients at over 100 sites in Europe, North and South America and Asia. The preliminary safety analyses showed the five most common adverse reactions were hypertension, diarrhea, decreased appetite, decreased weight and nausea. Based on positive clinical results, Eisai will submit marketing authorization applications for lenvatinib to health authorities in the U.S., Japan and Europe.

Medivation and Astellas Pharma released results of a phase III trial of enzalutamide in patients with chemotherapy- naïve metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms. The trial is a randomized, double-blind, placebocontrolled, multi-national trial that enrolled more than 1,700 patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. placebo. Treatment with enzalutamide demonstrated a statistically significant overall survival benefit compared with placebo treatment. Enzalutamide reduced the risk of death by 29% (HR=0.71). Treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19). Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35). Enzalutamide extended the median time to PSA progression from 2.8 months (placebo) to 11.2 months (HR= 0.169). Nearly four out of five patients in the enzalutamide group experienced a PSA decline of 50% or more, compared to less than 4% in the placebo group (78% vs. 3.5%). Regulatory applications to the FDA will be filed in early 2014.

February 10, 2014

Pfizer issued results of a phase II trial of palbociclib for the treatment of human epidermal growth factor receptor 2 negative (HER2-) locally advanced or newly diagnosed metastatic breast cancer. The phase II, multi-center trial, with 101 global sites participating, was designed to assess the PFS of palbociclib (125mg once daily for three out of four weeks in repeated cycles) in combination with letrozole v. letrozole alone (2.5mg once daily on a continuous regimen) in post-menopausal women with ER+, HER2- advanced breast cancer. PFS is comprised of time from randomization to time of disease progression or death from any cause. A randomized, global phase III trial (PALOMA-2) in this patient population is currently enrolling patients.

January 6, 2014

Takeda Pharmaceutical issued results of a phase III study of VELCADE (bortezomib) for the treatment of multiple myeloma (MM) in previously untreated patients. Results showed a higher cumulative dose suggests improved overall survival (OS) (hazard ratio [HR] 0.53; p<0.0001). Patients who received a cumulative dose of VELCADE of 39mg/m2 or greater lived 20 months longer on average than those who received lower cumulative doses (median OS 66.3 months and 46.2 months, respectively). Patients (n=340) treated with the VELCADE-melphalan-prednisone regimen received up to nine six-week cycles (up to 54 weeks) of the combination therapy (cycles 1-4: VELCADE 1.3mg/m2 IV, days 1, 4, 8, 11, 22, 25, 29, 32; cycles 5-9: VELCADE 1.3mg/m2 IV, days 1, 8, 22, 29; all cycles: melphalan 9mg/m2 and prednisone 60 mg/m2). The maximum planned dose of VELCADE was 67.6mg/m2, including 41.6mg/m2 during cycles 1-4 and 26mg/m2 during cycles 5-9. The median cumulative VELCADE dose received was 39mg/m2. OS was longer in patients in the higher (=39 mg/m2) v. lower (<39 mg/m2) cumulative dose group (median 66.3 v. 46.2 months; HR 0.53; p<0.0001). The HR for OS between the two groups, adjusted for age differences, that were significant between the two groups, was 0.56 (p=0.0002). A landmark analysis showed that in patients who survived past the 180-day threshold, OS was longer in the higher (=39mg/m2) v. lower (<39mg/m2) cumulative dose group (median 60.4 v. 50.3 months; HR 0.71; p=0.04).

December 9, 2013

Oncolytics Biotech reported results of Reolysin in combination with carboplatin and paclitaxel in patients with second-line platinum-refractory, taxane-naïve head and neck cancers. The double-blinded, randomized study enrolled 167 patients and showed a median PFS of 94 days in the test arm (n=62), v. 50 days in the control arm (n=56). Patients were evaluated for progression at the first scheduled post-treatment scan (performed at six weeks, post-cycle two of therapy). Of 62 patients on the test arm, 32.3% had progressed, compared with 51.8% of the 56 patients on the control arm (p=0.04). Of 86 patients with measurable disease at the first post-treatment scan, the test arm (n=48) had a statistically significant increase in tumor shrinkage over the control arm (n= 38; p=0.049).

Threshold Pharmaceuticals issued results of a phase I trial of TH-302 in combination with Avastin (bevacizumab) in patients with recurrent glioblastoma following bevacizumab failure. No dose-limiting toxicity has been reported to date at doses of TH-302 up to 670mg/m2 plus bevacizumab at 10mg/m2 every two weeks. A total of 19 patients have been enrolled in the ongoing trial. Of 14 patients evaluable for tumor response, the median time to progression was 86 days. 46% (95% CI: 18%-74%) of patients were alive without disease progression after three months of treatment. Preliminary data in 14 patients showed TH-302 in combination with bevacizumab was associated with a median time to progression of 2.8 months. One patient achieved a complete response and two patients achieved partial responses. No grade 4 adverse events were observed at any dose. Two grade 3 adverse events were observed at 340mg/m2 and 670mg/m2 of skin ulceration and thrombocytopenia, respectively. The study is continuing to enroll patients.

December 2, 2013

Merck issued results for a phase Ib trial of MK-3475 for the treatment of advanced melanoma. The trial is an ongoing, multi-center, single-arm, open-label study evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma)—predominantly lung and melanoma. Three dosing regimens of MK-3475 were evaluated: 10mg/kg every two weeks, 10mg/kg every three weeks or 2mg/kg every three weeks. The overall response rate at five months was 41% (CI 95%: 32 to 51%); 88% (43/49) of patients with a partial or complete response showed no evidence of disease progression. The maximum ongoing duration of response recorded was 65 weeks (range 8+ to 65+). The disease control rate across doses for patients in the melanoma cohort was 61% (CI 95%: 52 to 70%), and median progressionfree survival at time of analysis was 36 weeks. The company plans to initiate combination trials this year and in early 2014.

November 18, 2013

Angiochem released results of a phase II study of ANG1005 in 80 HER2-positive and HER2-negative breast cancer patients with brain metastases. Two doses, 650mg/m2 (n=13) and 550mg/m2 (n=67), were evaluated for intracranial anti-tumor responses including response rate, progression-free survival (PFS) and overall survival (OS). ANG1005 adverse events included neutropenia, fatigue, peripheral neuropathy and mucosal inflammation. HER2-positive patients (n=36) achieved PR’s (9, 25%) and stable disease (SD) (18, 50%) thereby demonstrating disease control in 75% of those patients. At 550mg/m2, three month PFS was 71% with a median PFS of 128 days and OS at six months of 82%. Her2-negative patients (n=44) achieved PR’s (5, 11%) and SD (17, 32%), demonstrating disease control in 50% of patients. In addition, at 550mg/m2, three months of PFS was 35% with a median PFS of 84 days and OS at six months of 60%. Angiochem will advance ANG1005 into a phase II clinical study in patients with recurrent high grade gliomas and a phase II clinical study in HER2-positive breast cancer patients with brain metastases.

November 11, 2013

Medivation and Astellas Pharma reported results of a phase III trial of enzalutamide in 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. The randomized, double-blind, placebo-controlled, multinational trial enrolled patients at sites in the U.S., Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial was designed to evaluate enzalutamide at a dose of 160mg taken orally once daily v. placebo. Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio=0.70; 95% confidence interval, 0.59- 0.83). Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with placebo (p<0.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (Hazard Ratio=0.19; 95% confidence interval, 0.15-0.23). The percentage of patients alive in the enzalutamide arm was 72%, as compared with 65% in the placebo arm, at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% confidence interval, 31.5 months-upper limit not yet reached) v. 30.2 months (95% confidence interval, 28.0 months-upper limit not yet reached) for patients receiving placebo. Medivation and Astellas will initiate meetings with and submissions to regulatory agencies beginning in early 2014.

October 28, 2013

Acacia Pharma issued results from a phase II study of APD515 for the treatment of xerostomia (dry mouth) in advanced cancer patients. The randomized, double-blind, placebo-controlled, cross-over trial was conducted in 11 centers in the U.K. and Denmark, and enrolled 32 patients with advanced cancer and a persistently dry mouth. Patients received a week of APD515 treatment and a week of placebo, in a randomly assigned order, with a week’s washout in between. Patients graded their symptoms before and after treatment and were asked to record which treatment week they preferred. Patients’ unstimulated salivary flow was measured before and after each treatment period. Subjective scoring was done on a standard 100mm visual analogue scale, where 0 represented no dryness and 100 the worst dryness possible. The average score for mouth dryness was 26.01 after treatment with APD515 and 43.52 after placebo (p=0.0005). Other subjective scores, for oral comfort, difficulty speaking and difficulty swallowing, all showed a significant improvement for APD515 over placebo. The overall number of adverse events was low, with no significant difference between APD515 and placebo.

September 9, 2013

Incyte issued results of a phase II trial of ruxolitinib, its oral JAK1 and JAK2 inhibitor, in combination with capecitabine in patients with recurrent or treatment refractory metastatic pancreatic cancer. The randomized, double-blind, placebo-controlled trial enrolled 136 patients. The hazard ratio (HR) for overall survival (OS) in the intent to treat population was 0.79 (one-sided p=0.12), and in a pre-specified subgroup analysis conducted in patients identified prospectively as most likely to benefit from JAK pathway inhibition, the HR for OS was 0.47 (one-sided p=0.005). Within this subgroup of patients, which represented 50% of the randomized population, six-month survival in the ruxolitinib arm was 42% v. 11% for placebo. Durable tumor responses were observed only in patients receiving ruxolitinib, and ruxolitinib-treated patients achieved a significant improvement in body weight relative to placebo. A phase III trial will be reviewed with the FDA.

August 19, 2013

Boehringer Ingelheim issued results of a phase III study of afatinib in patients with advanced non-small cell lung cancer (NSCLC). Data from the LUX-Lung 3 trial demonstrate superiority of afatinib over chemotherapy considered best-in-class (pemetrexed/cisplatin) in EGFR-mutation positive advanced NSCLC patients. Patients treated with afatinib lived for almost one year (progression-free survival (PFS) of 11.1 months) before their tumor started to grow again compared to just over half a year (PFS of 6.9 months) for those treated with chemotherapy. Patients taking afatinib with the most common EGFR mutations (del19 and L858R, accounting for 90% of all EGFR mutations) lived for well over a year without progression (PFS of 13.6 months) v. just over half a year (PFS of 6.9 months) for those in the comparator arm. Afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; P=0.007) and dyspnoea (HR, 0.68; P=0.015) and showed significantly better mean scores over time in global health status/QoL (P=0 .015) and physical (P<0.001), role (P=0.004) and cognitive (P=0.007) functioning compared with chemotherapy, as measured by standard questionnaires. The LUX-Lung clinical trial program currently involves eight studies designed to investigate the use of afatinib in various settings of advanced NSCLC, including head-to-head trials with the first-wave of reversible tyrosine kinase inhibitors.

August 12, 2013

GlaxoSmithKline issued results of a randomized, double-blind, phase III, placebo controlled trial of pazopanib monotherapy in women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose disease had not progressed after completing standard debulking surgery and first-line chemotherapy. After completion of five or more cycles of platinum-taxane chemotherapy, 940 patients were randomized 1:1 to receive 800mg pazopanib once daily or placebo for up to 24 months (median time from diagnosis to randomization was approximately seven months). Pazopanib treatment reduced the risk of disease progression or death by 23% (HR = 0.77; 95% CI: 0.64-0.91; p = 0.0021). The incidence of serious adverse events was higher in the pazopanib group compared to the placebo group (26% v. 11%). Regulatory applications will be submitted before 2014.

Immunomedics reported results of a phase Ib study of 90Y-labeled-clivatuzumab for the treatment of metastatic pancreatic cancer in 58 patients who had received at least two prior treatments. Patients were randomized to receive either 90Y-labeled-clivatuzumab once a week for three weeks at 6.5mCi/m2 with gemcitabine 200mg/m2 given weekly for four weeks (Arm A) or 90Y-labeled-clivatuzumab alone (Arm B). This treatment cycle was repeated every four weeks until unacceptable toxicity, patient deterioration or patient withdrawal. Patients were followed for one year or until death. The median overall survival (OS) for Arm A (N=27) was 119 days, an improvement over Arm B (N=26), with a median OS of 80 days (P=0.04). For the 23 patients who received multiple cycles of therapy, the median OS increased to 157 days in Arm A compared with 103 days in Arm B. Survival also was related to patients’ Karnofsky Performance Status (KPS) scores at study entry, increasing from a median of 79 days for patients with 80% KPS to 119 days for patients with 90% to 100% KPS. In contrast, increased number of prior treatments is a negative prognostic indicator for survival. The median OS decreased from 90 to 82 to 73 days for patients who received 2, 3 or 4 to 5 prior treatments, respectively. Phase III trials are planned for 2013 or the beginning of 2014 in the U.S. and the E.U.

July 29, 2013

Amgen released results from a phase II study of XGEVA (denosumab) in adults and skeletally mature adolescents diagnosed with giant cell tumor of bone (GCTB). In the international, open-label, phase II study enrolling 282 patients, there were three cohorts: patients with surgically unsalvageable GCTB (Cohort 1), patients with salvageable GCTB whose surgery was associated with severe morbidity (Cohort 2) and patients who transferred from a previous XGEVA GCTB study (Cohort 3). All three cohorts received subcutaneous XGEVA 120mg every four weeks with loading doses on days eight and 15. In Cohort 1, 96% (163/169) of patients had no disease progression after a median follow-up of 13 months. In Cohort 2, 74% (74/100) of patients required no surgery and 62% (16/26) of patients who had surgery underwent a less morbid procedure than planned. XGEVA was approved June 13 by the FDA for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity.

Bayer HealthCare issued results from a phase III study of Xofigo in castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. The randomized, double-blind, placebo-controlled, international study enrolled 921 patients in 100 centers in 19 countries. Patients were stratified based on their baseline alkaline phosphatase (ALP) level, current bisphosphonate use and whether or not they had received docetaxel prior to enrollment. Treatment consisted of up to six intravenous injections separated by four weeks. Xofigo improved overall survival (OS) at the prespecified interim analysis (HR=0.695, [95% CI: 0.552-0.875], p=0.00185); median OS was 14.0 months with Xofigo (95% CI: 12.1-15.8) vs. 11.2 months with placebo (95% CI: 9.0-13.2). These findings were supported by an exploratory analysis performed before patient crossover with an additional 214 events in which Xofigo showed improvement in OS (HR=0.695, [95% CI: 0.581-0.832]); median OS was 14.9 months in the Xofigo arm (95% CI: 13.9-16.1) v. 11.3 months in the placebo arm (95% CI: 10.4-12.8). These data supported the FDA approval of Xofigo injection in May.

July 1, 2013

Amgen reported results from a phase III trial of trebananib plus paclitaxel v. placebo plus paclitaxel for the treatment of recurrent ovarian cancer. This global, multicenter, randomized, double-blind, placebo-controlled study enrolled 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15mg/kg of intravenous trebananib weekly plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80mg/m of intravenous paclitaxel weekly (three weeks on, one week off). The trial met its primary endpoint of progression-free survival (PFS). A statistically significant difference was observed in PFS with a 34% reduction in the risk of disease progression or death (HR = 0.66, 95% CI, 0.57, 0.77, p<0.001). The median PFS was 7.2 months in the trebananib arm v. 5.4 months in the control arm.

June 24, 2013

Novartis reported results from a phase I trial of LDK378 for anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) in patients who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. This single-arm study enrolled 114 patients. The results showed an overall response rate of 60% in patients with ALK+ NSCLC taking LDK378 (750 mg/day), which includes patients who had progressed during or after crizotinib therapy (overall response rate of 59%) and those who were crizotinib-naive (overall response rate of 62%). 78 patients were treated at 750mg/day; 36 patients were treated with LDK378 at 400-750mg/day. The median duration of response for patients treated at 400mg/day or higher (n=66) was 8.2 months (95% confidence interval [CI], 6.9-NE), with a median progression-free survival of 8.6 months (95% CI; 5.7-9.9). The six-month duration of response rate at 750mg/day was 61% (95% CI; 34.9-78.8). This trial will serve as the basis for the first regulatory filing, anticipated in early 2014.

June 17, 2013

DelMar Pharmaceuticals reported results from a phase I/II trial of VAL-083 (dianhydrogalactitol) for the treatment of recurrent malignant glioma and progressive secondary brain tumors. Of the three cohorts of patients currently enrolled, all have failed standard therapies and have no viable treatment options. The subjects received VAL-083 at a dose of 1.5mg/m; 3.0mg/m and 5.0mg/m. At these doses, 25% (2/8) of GBM patients and 17% (1/6) of secondary-progressive brain cancer patients showed stable disease or tumor regression in response to treatment. VAL-083 therapy is well tolerated in glioblastoma multiforme (GBM) and secondary-progressive brain tumor patients with no drug-related serious adverse events at doses studied to date. DelMar plans to split the protocol into two separate studies: one focusing solely on refractory glioblastoma and the other focusing on metastatic brain cancers.

Halozyme Therapeutics reported results from a phase Ib trial of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) for the treatment of stage IV metastatic pancreatic cancer. The single-arm phase Ib trial enrolled 28 stage IV treatment naïve pancreatic ductal adenocarcinoma patients. The overall response rate (complete response + partial response) by RECIST 1.1 criteria was 42% (95% CI 22-62) for those treated at therapeutic dose levels of PEGPH20 (1.6 and 3.0μg/kg) as assessed by an independent radiology review (n=24). Additionally, in subjects with high levels of hyaluronan (HA), a substance found in a protective matrix that surrounds many pancreatic cancers, the overall response rate was 64% (seven of 11 subjects with available biopsy). Moreover, 43% (six of 14 subjects) saw a reduction of at least 70% in serum carbohydrate antigen 19-9 (CA 19-9), a biomarker that often correlates with tumor cell burden. Treatment was generally well tolerated, and the adverse event profile was consistent with those seen in previous studies of PEGPH20 as a single agent and as previously reported for gemcitabine alone. The most common adverse events were muscle spasms, myalgia and arthralgia (all grade 1/2). There was no evidence of new toxicities when used in combination with gemcitabine. The results support the dosing regimen at 3μg/kg, being used in the phase II trial.

June 10, 2013

Boehringer Ingelheim issued results from a phase III trial of LUME-Lung 1 for the treatment of advanced non-small cell lung cancer (NSCLC). This randomized, openlabel, double-blind study enrolled 1,314 patients with locally advanced or metastatic (stage IIIb/IV or recurring) NSCLC after first-line therapy. The subjects received nintedanib 200mg BID plus docetaxel 75mg/m(2) once a day for three weeks (n=655), or docetaxel plus placebo (n=659). LUME-Lung 1 improved progression-free survival (PFS)—the primary endpoint—as a second-line treatment in patients with NSCLC compared to docetaxel alone. Secondary endpoints included overall survival. Results showed patients treated with nintedanib plus docetaxel lived for a median of 3.4 months before their tumor started to grow again, versus 2.7 months with docetaxel alone (HR 0.79; p=0.0019). The most common adverse events (AEs) of any grade in the nintedanib combination and docetaxel alone groups were diarrhea (42.3% v. 21.8%, respectively) and ALT elevations (28.5% v. 8.4%, respectively). Incidence of > grade 3 AEs was 71.3% in patients treated with nintedanib plus docetaxel compared to 64.3% with docetaxel alone. A higher incidence of > grade 3 diarrhea and elevated ALT were observed in patients treated with nintedanib plus docetaxel compared to docetaxel alone (> grade 3 diarrhea: 6.6% v. 2.6%; elevated ALT: 7.8% v. 0.9%). Incidence of > grade 3 hypertension, bleeding and thrombosis were similar in both treatment arms. There was a 1% difference in discontinuation between the treatment arms, with 22.7% of patients stopping treatment with nintedanib plus docetaxel versus 21.7% with docetaxel alone.

Novartis reported results from a phase III trial of Afinitor for the treatment of HER2 positive advanced breast cancer. This randomized, double-blind study of everolimus plus trastuzumab and vinorelbine conducted at 159 clinical trial sites globally included 569 women with HER2 positive locally advanced or metastatic breast cancer who were previously treated with a taxane and were resistant to trastuzumab. Subjects received either everolimus 5mg/day orally or placebo, plus weekly vinorelbine 25mg/m IV and weekly trastuzumab 2mg/kg IV following a loading dose of 4mg/kg. The primary endpoint of significantly extended progression-free survival (PFS) when compared to treatment with placebo plus trastuzumab and vinorelbine was met. Final PFS results showed adding everolimus to the standard treatment of trastuzumab and vinorelbine reduced the risk of disease progression by 22% (hazard ratio=0.78 [95% confidence interval (CI):0.65 to 0.95]; p<0.01). Median time to progression was 7.0 months in the everolimus combination arm and 5.8 months in the placebo combination arm. Adverse events were consistent with the known safety profile of everolimus. The most common all-grade adverse reactions (incidence >30%) were neutropenia, stomatitis, anemia, leukopenia, fatigue, pyrexia, diarrhea, nausea, decreased appetite and constipation.

May 20, 2013

Syndax Pharmaceuticals published results from a phase II trial of entinostat for the treatment of estrogen receptor-positive (ER+) breast cancer in the Journal of Clinical Oncology. This randomized, double-blind, placebo-controlled study, ENCORE 301, enrolled 130 postmenopausal women with ER+ breast cancer whose cancer had progressed after treatment with a nonsteroidal aromatase inhibitor. Subjects received 25mg exemestane daily plus 5mg entinostat once per week, or 25mg exemestane plus placebo. Based on intent-to-treat analysis, patients treated with entinostat saw improved median progression-free survival to 4.3 months versus 2.3 months in patients treated with placebo (hazard ratio 0.73; 95% confidence interval, 0.50 to 1.07; one-sided p=.055; two-sided p=.11). Overall survival was an exploratory endpoint, and median survival improved to 28.1 months in entinostat-treated patients versus 19.8 months in placebo-treated (hazard ratio 0.59; 95% confidence interval, 0.36 to 0.97; p=.036). Entinostat was well tolerated. The most frequent adverse events were fatigue and neutropenia. Based on this data, Syndax Pharmaceuticals is working to move entinostat into a confirmatory pivotal study this fall.

May 13, 2013

Amgen issued results from a phase III head-to-head trial of Vectibix (panitumumab) versus Erbitux (cetuximab) for chemorefractory metastatic colorectal cancer (mCRC). This global, randomized, parallel-assignment, open-label, non-inferiority study enrolled 1,010 patients with mCRC with wild-type KRAS tumors. Subjects received 6mg/kg of intravenous Vectibix every 14 days or 400mg/m2 of an initial dose of intravenous Erbitux followed by 250mg/m2 of intravenous Erbitux every seven days. Data demonstrated the estimated overall survival hazard ratio (Vectibix/Erbitux) was 0.966 (95% CI: 0.839, 1.113) favoring the Vectibix arm. Vectibix was well tolerated. Overall, the relative adverse event profiles were as anticipated for each of the anti-EGFR therapies studied, including known events such as rash, diarrhea and hypomagnesemia.

April 15, 2013

Navidea Biopharmaceuticals issued interim results from a phase III trial of Lymphoseek (technetium 99m tilmanocept) for identifying sentinel lymph nodes (SLNs) in patients with head and neck squamous cell carcinoma. This open-label, multicenter, within-patient study, NEO3-06, enrolled 80 patients with head and neck squamous cell carcinoma. After receiving a Lymphoseek injection, 39 of the 80 patients were determined to have pathology-positive lymph nodes. Results demonstrated of these 39 patients, Lymphoseek accurately identified 38, for an overall False Negative Rate (FNR) of 2.56%, which was statistically significant (p=0.0205) and met the statistical threshold for success of the primary endpoint. Moreover, multiple-level nodal dissection of patients in the trial with cancer-positive lymph nodes led to an average removal of 38 lymph nodes per patient, whereas Lymphoseek on average led to the removal of approximately four lymph nodes, representing a substantial reduction in potential morbidity for patients with head and neck cancer undergoing sentinel lymph node biopsy. Based on these data, Navidea Biopharmaceuticals will evaluate the possibility of filing a Supplemental New Drug application (sNDA) later this year.

March 25, 2013

GTx published results from a phase II trial of enobosarm for the treatment of muscle wasting and physical function in cancer in The Lancet Oncology. This multi-center, randomized, double-blind, placebo-controlled study enrolled 159 patients who had been diagnosed with non-small cell lung cancer (NSCLC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or breast cancer and who had not yet begun chemotherapy or were between chemotherapy cycles. Subjects received 1mg or 3mg enobosarm orally daily, or placebo, for up to 113 days. Data demonstrated patients receiving enobosarm (either 1mg or 3mg) showed a statistically significant increase from baseline to Day 113/end of trial in total lean body mass and a significant improvement from baseline in the time and power to climb 12 stairs. Patients receiving placebo during the same period did not show significant increases in total lean body mass or in physical function. Although the trial was not powered to assess survival, in a post-hoc analysis the survival hazard ratio for patients receiving enobosarm 1mg versus placebo was 0.80 and for those receiving enobosarm 3mg versus placebo was 0.70, representing a 20% and 30% improvement in survival, respectively. Enobosarm was well tolerated. The most frequent adverse events were similar among placebo and treatment groups. Based on this data, GTx has initiated two phase III trials of 3mg enobosarm in muscle wasting in patients with NSCLC.

March 4, 2013

Peregrine Pharmaceuticals issued results from a phase II trial of bavituximab for the treatment of non-small cell lung cancer (NSCLC). This Peregrine's randomized, double-blind, placebo-controlled study enrolled 121 patients with previously treated locally advanced or metastatic second-line NSCLC. Subjects received bavituximab 3mg/kg plus docetaxel or placebo plus docetaxel. Results showed a meaningful improvement in median overall survival of 11.7 months in the bavituximab plus docetaxel arm compared to 7.3 months in the control arm (HR=0.73; p value=0.217). Persistent separation in the survival curves was observed with response rates and progression-free survival also favoring the bavituximab plus docetaxel. Bavituximab was well tolerated. The most frequent adverse events were similar between both treatment arms. Based on these data, Peregrine is preparing for an end-of-phase II meeting with the FDA.

February 25, 2013

Argos Therapeutics reported results from a phase II trial of AGS-003 for metastatic renal cell carcinoma (mRCC). This open-label study enrolled 21 patients with unfavorable risk mRCC and with an expected survival of approximately 15 months. Subjects received standard six-week cycles of sunitinib plus AGS-003, administered every three weeks for five doses, and then every 12 weeks until progression. Results showed median overall survival was 30.2 months. When analyzed by baseline Heng risk status, the median overall survival for intermediate risk patients (n=11) has not been reached, but is estimated to be longer than 39.5 months with continued follow-up. Median overall survival for poor risk patients (n=10) was 9.1 months. Of the 21 patients who participated in the study, seven (33%) patients are still alive after nearly four years or longer following study registration. Argos Therapeutics is currently enrolling patients in a global phase III study of AGS-003.

Progenics Pharmaceuticals released results from a phase I trial of PSMA ADC for prostate cancer. This open-label, dose-escalation study enrolled 52 men with metastatic castration-resistant prostate cancer that had progressed despite prior treatment with taxane-based chemotherapy regimens. Subjects received nine different dosing levels of PSMA ADC administered at three-week intervals for 12 weeks. Significant antitumor activity was observed across doses ranging from 1.8mg/kg to 2.8mg/kg. PSMA ADC was generally well tolerated in patients at doses up to and including 2.5mg/kg, the maximum tolerated dose. Dose limiting toxicities, primarily neutropenia, were seen at 2.8mg/kg. The most frequent adverse events were anorexia and fatigue. Progenics Pharmaceuticals initiated a phase II, open-label, multicenter study of PSMA ADC.

February 18, 2013

AVEO Oncology and Astellas Pharma reported results from a phase III trial of tivozanib compared to sorafenib for the treatment of advanced renal cell carcinoma (RCC). This global, randomized study, TIVO-1, enrolled 517 patients with RCC. Subjects received either tivozanib or sorafenib. The final overall survival (OS) analysis showed a median OS of 28.8 months (95% confidence interval [CI]: 22.5–NA) for tivozanib versus a median OS of 29.3 months (95% CI: 29.3–NA) for the comparator arm, sorafenib. No statistical difference between the two arms (HR=1.245, p=0.105) was observed. Patients randomized to the sorafenib arm were eligible to cross over to tivozanib therapy under a separate protocol after radiographic confirmation of disease progression. No crossover protocol was available for patients randomized to the tivozanib arm. Tivozanib was well tolerated. Based on these data, AVEO and Astellas have filed a New Drug Application (NDA) for tivozanib for the treatment of RCC.

Peregrine Pharmaceuticals released results from a phase II trial of bavituximab in combination with gemcitabine Stage IV pancreatic cancer. This open-label, randomized study enrolled 70 patients with previously untreated, advanced Stage IV pancreatic cancer. Subjects received either bavituximab in combination with gemcitabine, or gemcitabine alone. Data demonstrated the combination of bavituximab and gemcitabine resulted in more than a doubling of overall response rates (ORR) and an improvement in overall survival (OS) when compared with gemcitabine. Subjects treated with a combination of bavituximab and gemcitabine had a 28% tumor response rate as compared to 13% in the control arm. Median OS, the primary endpoint of the trial, was 5.6 months for the bavituximab plus gemcitabine arm and 5.2 months for the control arm (HR=0.75). Bavituximab was generally safe and well tolerated, with similar adverse events occurring in both arms. Peregrine is evaluating the next steps for advancing the bavituximab pancreatic program to include combination with other cancer agents. Bavituximab is currently being evaluated in patients with non-small cell lung, breast, prostate, liver and rectal cancers in combination with approved chemotherapies and radiation.

February 4, 2013

Amgen issued results from a phase III trial of Neulasta (pegfilgrastim) for the treatment of colorectal cancer. This multinational, randomized, double-blind, placebo-controlled trial enrolled 845 patients receiving FOLFOX or FOLFIRI and bevacizumab for the first-line treatment of locally-advanced or metastatic colorectal cancer. Subjects received 6mg of Neulasta, or placebo, at least 24 hours after each cycle of chemotherapy. Results showed the study met its primary endpoint: Neulasta significantly reduced the incidence of febrile neutropenia (low white blood cell count accompanied by a fever). In the study, the incidence of grade 3 or 4 febrile neutropenia in patients receiving Neulasta across the first four cycles of chemotherapy was 2.4%, compared to 5.7% in the placebo group (OR=0.41, p=0.014). A similar incidence of grade 3 or higher adverse events was seen in both arms of the trial (28% placebo; 27% Neulasta). The drug was well tolerated. Amgen did not note its plans for Neulasta.

January 28, 2013

Celgene International issued results from a phase III trial of Abraxane in combination with gemcitabine for the treatment of metastatic pancreatic cancer. This open-label, randomized, international study, MPACT, enrolled 861 treatment-naïve patients with metastatic pancreatic cancer. Subjects received 125mg/m2 Abraxane plus 1000mg/m2 gemcitabine for three weeks, followed by a week of rest, or 1000mg/m2 gemcitabine alone for seven weeks, followed by a week of rest. Data demonstrated a statistically significant improvement in overall survival in the Abraxane/gemcitabine arm compared to patients receiving gemcitabine alone (median of 8.5 vs. 6.7 months) (HR 0.72, p=0.000015). Results showed the Abraxane/gemcitabine arm demonstrated a 59% increase in one-year survival (35% versus 22%, p=0.0002) and demonstrated double the rate of survival at two years (9% versus 4%, p=0.02) as compared to gemcitabine alone. Furthermore, the Abraxane/gemcitabine arm demonstrated a 31% reduction in the risk of progression or death with a median progression-free survival of 5.5 versus 3.7 months (HR 0.69, P=0.000024) and an overall response rate of 23% compared to 7%. The drug was well tolerated. The most frequent adverse events were neutropenia, fatigue and neuropathy. Based on these results, Celgene International plans to submit dossiers for registration in the U.S. and Europe during the first half of 2013, followed by submissions in other countries/regions during the second half of 2013.

January 7, 2013

Bristol-Myers Squibb reported results from a phase II trial of elotuzumab in combination with lenalidomide and low-dose dexamethasone for the treatment of multiple myeloma. This randomized, multi-center, open-label study enrolled patients with previously treated multiple myeloma. Subjects received either 10mg/kg or 20mg/kg of elotuzumab intravenously on days 1, 8, 15 and 22 of a 28-day cycle in the first two cycles, and then on days 1 and 15 of subsequent cycles. Subjects also received lenalidomide 25mg PO daily on days 1 to 21 and dexamethasone 40mg PO weekly. Results demonstrated in the 10mg/kg arm, median progression-free survival (PFS) was not reached after 20.8 months of follow up (n=36) and the objective response rate (ORR; according to the International Myeloma Working Group response criteria) was 92%. Of patients who received elotuzumab at a dose of 20mg/kg, median PFS was 18.6 months (n=37) and ORR was 76%. Elotuzumab was well tolerated. The most frequent adverse events were lymphopenia, neutropenia, thrombocytopenia, anemia, leukopenia, hyperglycemia, pneumonia, diarrhea, fatigue and hypokalemia. BMS also is studying elotuzumab in two phase III trials for treatment of relapsed/refractory multiple myeloma.

December 17, 2012

Boehringer Ingelheim issued preliminary results from a phase II trial of volasertib for the treatment of acute myeloid leukemia (AML). This open-label study enrolled 87 patients with newly-diagnosed AML who were considered ineligible for intensive remission induction therapy. Subjects received volasertib in combination with low-dose cytarabine (LDAC) (n=42) or LDAC alone (n=45). Results showed objective responses were observed in 31% of patients (13/42) treated with the combination of volasertib plus LDAC compared with 13.3% of the patients (6/45) treated with LDAC alone (odds ratio: 2.91; p=0.0523). The median time to remission was 71 (29158) days and 64 (30125) days, respectively. Data also showed that in patients treated with the combination of volasertib plus LDAC, the median event free survival was approximately 5.6 months (170 days) compared with approximately 2.3 months (69 days) in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, 0.93; p=0.0237). Volasertib was well tolerated. The most frequent adverse events were gastrointestinal events, general events, infections, febrile neutropenia, metabolism/nutrition events and respiratory/thoracic/mediastinal events. Based on these data, Boehringer Ingelheim intends to begin recruitment of a phase III study of volasertib in combination with LDAC compared with LDAC alone in early 2013.

Celgene International released results from a phase I trial of CC-486 (oral azacitidine) for the treatment of myelodysplastic syndromes (MDS). This multi-arm study enrolled 53 patients with lower-risk MDS who were red blood cell transfusion-dependent and/or thrombocytopenic. Subjects received 300mg of CC-486 once daily for either 14 or 21 days of each 28-day cycle. After a median of seven treatment cycles for the 14-day treatment arm and five for the 21-day treatment arm, the overall response rate was 42.3% (11/26) and 37.0% (10/27), respectively. Additionally, the percentage of patients showing any hematologic improvement was 26.9% in the 14-day arm and 29.6% in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 56 days was 53.5% in the 14-day arm and 40.0% in the 21-day arm. The percentage of patients who sustained RBC transfusion independence for 84 days was 20% in the 14-day arm and 33.3% in the 21-day arm. CC-486 was well tolerated. The most frequent adverse events were anemia, thrombocytopenia, neutropenia and febrile neutropenia. Based on these and other early-stage data evaluating CC-486, Celgene plans to initiate two phase III studies (QUAZAR program) evaluating this oral agent in lower-risk MDS and acute myeloid leukemia by the end of 2012.

December 10, 2012

ARIAD Pharmaceuticals released results from a phase I trial of ponatinib for the treatment of resistant and refractory chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This dose-escalation study enrolled 81 patients with resistant hematologic cancers, including 60 patients with CML and five patients with Ph+ ALL, who had become resistant to one or more tyrosine kinase inhibitors. Results showed that after 73 weeks, 72% of patients (31 of 43) with chronic-phase CML had a major cytogenetic response (MCyR), including 92% (11 of 12) who had the T315I gatekeeper mutation, the most common mutation among resistant patients. In addition, of 22 patients with accelerated-phase or blast-phase CML or Ph+ ALL, 36% (8 of 22) had a major hematologic response and 32% (7 of 22) had aMCyR. The drug was well tolerated. The most frequent adverse events were rash, thrombocytopenia, arthralgia, increased lipase, fatigue, acneiform dermatitis dry skin and nausea. ARIAD did not disclose its plans for ponatinib.

November 28, 2012

Aeterna Zentaris reported results from a phase I trial of perifosine combined with temsirolimus for the treatment of malignant glioma. This combination, dose-ranging study enrolled 32 patients with recurrent or progressive malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma and transformed low-grade gliomas with median Karnofsky Performance Status 80. Subjects either received a 600mg or 900mg dose of perifosine on day one, followed by a nightly dose of 100mg of perifosine. All subjects also received 15mg to170mg of temsirolimus once weekly. Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12). The most frequent adverse events were hypophosphatemia, hypocholesterolemia and hypertriglyceridemia. The maximum tolerated dose was not defined, so Aeterna Zentaris is creating expansion cohorts.

OncoSec Medical issued preliminary results from a phase II trial of ImmunoPulse for the treatment of metastatic melanoma. This single-arm, open-label and multi-center study has enrolled 13 patients with stage III or IV cutaneous and in-transit metastatic melanoma, of 25 patients expected. Subjects received a maximum dose of 1.5mg of DNA IL-12 via ImmunoPulse on days one, five and eight, applied to up to four lesions. Subjects also received electroporation treatment. Results suggested that ImmunoPulse is able to induce regression or stabilization of distant untreated metastases following a single cycle of treatment. Ninety-five percent of treated lesions demonstrated response at day 39 (5% progressive disease, 14% stable disease (SD), 42% partial response (PR), 39% complete response (CR)). All treated lesions at day 90 (5% SD, 50% PR, 45% CR), and at day 180 (33% PR, 67% CR) demonstrated a response. At day 180, two subjects were evaluable for the primary endpoint of objective overall response (ORR). One patient has a confirmed stable disease, and the second patient has a confirmed complete response of all treated and untreated lesions. ImmunoPulse and DNA IL-12 were well tolerated. The most frequent adverse events were generally limited to transient pain related to electroporation treatment. OncoSec Medical will continue the phase II study, which it expects to be completed by the end of 2012.

November 12, 2012

MorphoSys and Xencor released results from a phase I/IIa trial of MOR208 (MOR00208/XmAb5574) for the treatment of tumor activity. This dose-ranging study enrolled patients with high-risk, heavily pretreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Subjects received doses ranging from MOR208 0.3mg/kg to 12mg/kg as an intravenous infusion on days 1, 4, 8, 15 and 22 in cycle one, and on days 1, 8, 15 and 22 in cycle two. Overall response rate by International Working Group on CLL (IWCLL) 2008 criteria was 11%, which utilizes more rigorous CT scan reduction of internal lymph nodes not previously required in older historic studies. Using IWCLL 1996 response criteria resulted in a response rate of 42%. MORE208 was well tolerated and found safe. The most frequent adverse events were mild to moderate infusion reactions usually with the first dose. Based on these results, MorphoSys plans to commence phase II studies of MOR208 in B-cell malignancies in the near future.

November 5, 2012

Alliance for Clinical Trials in Oncology released results from a phase III trial of doxepin for the treatment of head and neck cancer. This multi-institution, randomized, double-blind, placebo-controlled study enrolled 140 patients who were also receiving radiation therapy for their head and neck cancer (>50.0Gy), which involved more than one-third of the oral cavity. Subjects received a single, blinded dose of doxepin rinse (doxepin 25mg in 5ml of water) or placebo on day one, and then crossed over to the opposite study group on a subsequent day. Results indicated that the addition of doxepin significantly decreased pain, which was measured by the area under the curve (AUC) on the pain scale over time. Patients who received doxepin reported a reduction in pain to a -9.1 versus -4.7 for those who received the placebo. Analysis of the crossover data revealed similar findings, with an AUC score of -7.9 in the doxepin group versus -5.6 in the placebo group. Sixty-four percent of patients elected to continue doxepin after the study was completed. Doxepin was well tolerated. The most frequent adverse events were stinging/burning, unpleasant taste and greater drowsiness.

Specialised Therapeutics Australia issued results from a phase III comparative trial of Abraxane versus standard chemotherapy for the treatment of metastatic melanoma. This randomized, open-label, international study enrolled 529 chemotherapy-naïve patients. Subjects received either Abraxane 150mg/m2 weekly for three out of four weeks, or dacarbazine 1000mg/m2 every three weeks. The Abraxane arm showed statistically significant improvement in progression-free survival (PFS) (4.8 months) compared to patients receiving dacarbazine chemotherapy (2.5 months) (HR:0.792; 95.1% CI: 0.631, 0.992; P=0.044). Data shows overall survival trends in favor of the Abraxane arm (12.8 months) compared to dacarbazine (10.7 months) (HR:0.831; 99.9% CI: 0.578, 1.196; P=0.094). The drug was well tolerated. The most frequent adverse events were neuropathy and neutropenia. Specialised Therapeutics Australia hopes to have Abraxane approved by the Therapeutic Goods Administration in Australia by 2014.

October 29, 2012

Celgene International reported results from a phase III trial of pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone for multiple myeloma. This multi-center, randomized, open-label study enrolled patients with relapsed and/or refractory multiple myeloma. Subjects in Arm 1 received 4mg pomalidomide on days 1-21 of each 28-day cycle, with patients 75 years or younger also receiving 40mg of low-dose dexamethasone and patients older than 75 receiving 20mg of low-dose dexamethasone on days 1, 8, 15 and 22 of each 28-day cycle, until disease progression. Subjects in Arm 2 received 40mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of each 28-day cycle if they were 75 years or younger, and patients older than 75 received 20mg high-dose dexamethasone on days 1-4, 9-12 and 17-20 of a 28-day cycle, until disease progression. The study met its primary endpoint of improvement in progression-free survival (PFS) at the PFS final analysis. Additionally, the study crossed the superiority boundary for overall survival (OS), a key secondary endpoint. As a result, patients who had not yet progressed in the high-dose dexamethasone arm should be crossed-over to the pomalidomide plus low-dose dexamethasone arm. Celgene has submitted an NDA application to the FDA, as well as an MAA application to the EMA.

October 15, 2012

Boehringer Ingelheim released results from a phase III trial of afatinib for the treatment of non-small cell lung cancer (NSCLC). This randomized, open-label study enrolled 345 previously untreated patients with EGFR mutation positive NSCLC. Subjects received afatinib or standard chemotherapy agents (pemetrexed/cisplatin) as first-line treatment. Data showed afatinib-dosed patients had a progression-free survival (PFS) of 11.1 months versus a PFS of 6.9 months for those receiving pemetrexed/cisplatin. NSCLC patients with tumors harboring the two most common EGFR mutations (del19 and L858R) receiving afatinib had a PFS of 13.6 months versus a PFS of 6.9 months for those in the comparator arm. The afatinib-dosed arm experienced an improvement in shortness of breath, cough and chest pain, a delay in deterioration of these symptoms, and overall improved quality of life. Afatinib was well tolerated. Boehringer Ingelheim has initiated two head-to-head trials comparing afatinib to Iressa (gefitinib) and Tarceva (erlotinib), to demonstrate any potential efficacy and safety superiority.

October 1, 2012

Cell Therapeutics reported results from a phase I trial of pacritinib (SB1518) for the treatment of relapsed/refractory lymphoma. This multi-arm, dose-finding study enrolled 34 patients with relapsed or refractory Hodgkin’s or non-Hodgkin’s lymphoma of any type except Burkitt’s or CNS lymphoma. Subjects received pacritinib ranging from 100mg to 600mg daily. Data showed the maximum dose was not met. Pacritinib inhibited JAK2 signaling at all dosing levels and FLT-3 inhibition were seen in most patients. Seventeen of the 34 patients (50%) had measurable decreases in target tumor measurements ranging from 4% to 70% shrinkage. Partial remissions were noted in three patients (mantle cell and indolent lymphoma), while 15 patients had stable disease. Median progression-free and overall survival was 120 and 130 days, respectively. Pacritinib was well tolerated. The most frequent adverse events were gastrointestinal. Based on these data, Cell Therapeutics will continue with efficacy studies of JAK/STAT pathway inhibitors, either alone or in combination regimens.

September 24, 2012

Jennerex reported results from a phase II trial of JX-594 for the treatment of hepatocellular carcinoma (HCC). This nonrandomized study enrolled 25 Asian patients with advanced HCC; 20 were refractory to sorafenib and were treated with an intravenous dose of JX-594, while the majority of patients then received sequential intra-tumoral doses of JX-594 at week one and three. The majority subsequently received treatment with sorafenib. The study met its primary endpoint of determining the safety of JX-594 followed by sorafenib in patients with advanced HCC. After six or 12 weeks, 59% had disease control as measured by modified RECIST and 75% had objective responses by Choi criteria. 85% of patients had disease control by mRECIST or Choi response. The sequential treatment regimen was well tolerated with transient flu-like symptoms, with the most common adverse event being transient leukopenia. Jennerex is planning several phase II studies of JX-594 in liver cancer, HCC and colorectal cancer.

September 17, 2012

ImmunoGen released results from a phase II trial of IMGN901, in combination with etoposide and carboplatin, for the treatment of small cell lung cancer (SCLC). This randomized, dose-finding study, NORTH, enrolled 120 patients. Subjects received etoposide 100 mg/m2 on days one through three every 21 days; carboplatin AUC5 or AUC6 on day one every 21 days; and IMGN901 ranging up to 112 mg/m2, administered on days one and eight every 21 days. Results showed that IMGN901 112 mg/m2, carboplatin AUC5 and etoposide 100 mg/m2 was the most effective dose. Of the 33 patients dosed with this regimen, 10 had an objective response and 24 (72.7%) had disease control (objective response or stable disease). IMGN901 was well tolerated. The most frequent adverse event was low grade peripheral neuropathy.

August 27, 2012

Medivation and Astellas Pharma published results from a phase III trial of enzalutamide for the treatment of metastatic castration-resistant prostate cancer. This international, randomized, double-blind, placebo-controlled study, AFFIRM, enrolled 1,199 men who had been previously treated with docetaxel-based chemotherapy. Subjects received enzalutamide 160mg once daily (as four 40mg capsules), or placebo. Data showed enzalutamide exhibited a statistically significant benefit in overall survival compared to placebo. Men treated with enzalutamide had a median overall survival of 18.4 months (95% confidence interval, 17.3 to not yet reached) compared to 13.6 months (95% confidence interval 11.3-15.8) for men treated with placebo (hazard ratio 0.63; p<0.0001), representing a 37% reduction in the risk of death. The drug was well tolerated. The most frequent adverse events were fatigue, diarrhea and hot flush. Seizure was reported in less than 1% of enzalutamide-treated patients. Neither Medivation nor Astellas noted its next steps for enzalutamide.

August 6, 2012

Advaxis released interim results from a phase II trial of ADXS-HPV for the treatment of with recurrent/refractory cervical cancer. This multi-arm, randomized study has enrolled 63 female patients thus far who have failed previous cytotoxic therapy. Subjects received ADXS-HPV (1x109 cfu) with or without cisplatin 40mg/m2 weekly for five weeks. The primary endpoint, survival, at months six, nine and 12 is 64%, 46% and 29%, respectively, while the National Comprehensive Network Guidelines cite historical 12-month survival data of 0%-22% with single agent therapy in this patient population. Thus far, ADXS-HPV has triggered five complete responses (three in the ADXS alone group; two in the ADXS+ cisplatin group) and six partial responses (three in the ADXS alone group; three in the ADXS+ cisplatin group). A complete response is defined as 100% elimination of tumor burden, whereas a partial response is defined as 30% or more reduction in tumor burden. The drug was well tolerated. Advaxis is continuing the trial in India, and the Gynecologic Oncology Group plans to conduct a phase II study of ADXS-HPV in a similar patient population in the U.S.

July 9, 2012

Synta Pharmaceuticals reported interim results from a phase IIb/III trial of ganetespib in combination with docetaxel for the treatment of advanced non-small cell lung cancer (NSCLC). This multi-arm, randomized, open-label phase IIb part of the GALAXY study enrolled 183 patients to date with stage IIIB/IV NSCLC who have progressed following one prior line of therapy. All subjects received a standard regimen of docetaxel 75mg/m2 on Day 1 of a 21-day cycle; subjects in the combination arm receive in addition ganetespib 150mg/m2 on Day 1 and 15. Both primary endpoints were met based on RECIST 1.1 criteria. Subjects with elevated baseline level of serum LDH (lactate dehydrogenase) who received a combination of ganetespib and docetaxel had a median PFS of 4.2 months, compared to 1.4 months in those treated with only docetaxel; subjects with a tumor KRAS mutation receiving the combination treatment had a median PFS of 4.2 months, while the docetaxel group had a PFS of 1.6 months. The treatment was well tolerated. The most frequent adverse events were neutropenia, diarrhea and fatigue. Synta Pharmaceuticals will continue to enroll more subjects in the phase IIb trial. The transition into phase III is expected later this year.

June 9, 2008

Celator released positive results from a phase II trial of CPX-1 for the treatment of colorectal cancer. This multi-center, open-label study enrolled 59 subjects who were placed in two arms: irinotecan-naive (IRI-naive) and irinotecan-refractory (IRI-refractory) and received 210 units/m2 of CPX-1 every two weeks. In the IRI-naive arm the overall response rate was 8% and the disease control rate (response or stable disease) was 65 percent. Median progression- free survival (PFS) was 3.9 months and six subjects had a greater than six month PFS. In the IRI-refractory arm the disease control rate was 45%; there were no reports of an objective response. The median PFS was 2.3 months and three subjects had a greater than six month PFS. The 210 unit/m2 dose produced more toxicities than seen in previous phase 1 studies, resulting in only 40 percent of the subjects receiving more than 80 percent of the planned dose intensity. Hence, treatment will be initiated at a lower dose in future studies. Based on the results Celator plans to move forward with the development of CPX-1.

February 4, 2008

Pro-Pharmaceuticals reported positive results from a phase II trial of Davant for the treatment of colorectal cancer. This trial enrolled twenty previously heavily treated subjects, all of whom had at least two previous chemotherapy treatments including; fluorpyrimidines, Irinotecan, Oxaliplatin and Avastin or Erbitux. All subjects received Davant (280 mg/m2) in combination with 5-fluorouracil (5-FU, 500 mg/m2), given four times monthly until disease progression or unacceptable toxicity. The median progression free survival was 8.4 weeks and one subject reported an objective response. Treatment was generally well tolerated. There were seven reports of serious adverse events, however only two of these, anemia and dehydration, were considered to be drug related. Based on the results, Pro-Pharmaceuticals plans to move forward with the development of Davant.

pSivida issued positive results from a phase IIa trial of Brachysil for the treatment of pancreatic cancer. This trial enrolled seventeen subjects with advanced inoperable pancreatic cancer. The subjects received BrachySil, injected directly into the primary tumors via endoscopic ultrasound, in combination with standard chemotherapy (gemcitabine). CT assessments of response were performed at weeks eight, sixteen and twenty four. The combination treatment was well tolerated, with no significant adverse events related to BrachySil. Data showed disease control in 82% of subjects and an overall median survival of three hundred and nine days. In addition, BrachySil was found to be easily deliverable by endoscopic ultrasound. Based on the results, pSivida plans to commence a phase II dose ranging study in the first quarter of 2008.

November 26, 2007

Thallion reported positive results from a phase I/II trial of ECO-4601 for the treatment of advanced cancers. The trial enrolled twenty-six subjects who were refractory to their respective standard of care therapy. ECO-4601 was administered in twenty-one day cycles consisting of a two week continuous intravenous infusion followed by a one week rest period. The trial was conducted in two portions. In the first portion, fourteen subjects received escalating doses ranging from 30 to 480mg/m2/day to assess safety, pharmacokinetics and maximum tolerated dose. In the second portion of the trial, twelve subjects were treated at the highest dose, 480mg/m2/day. Treatment was well tolerated and the maximum target dose was attained before the maximum tolerated dose was reached. Pharmacokinetic data demonstrated that estimated therapeutic plasma concentrations of ECO-4601 were reached at the higher doses and that ECO-4601 was rapidly eliminated from the bloodstream following infusion. In addition, six of seven subjects with refractory cancer who had completed six cycles of treatment achieved stable disease. Based on the results, phase II trials were expected to be initiated in early 2008.

June 9, 2003

Agennix and Veterans Affairs Medical Center reported positive results from two phase I/II trials investigating Lactoferrin (rhLF), a natural protein found in milk, for the treatment of solid tumors. Data showed that 53% of evaluable subjects (10 /19) demonstrated stable disease, three of which showed tumor shrinkage. In addition, 29 subjects completed dosing, with only one withdraw due to disease progression. The saftey portion of the studies enrolled 30 subjects and evaluated rhLF as a single agent for the treatment of solid non-resectable tumor cancer patients, who had progressed on standard chemotherapy. Subjects were administered one of four different doses of rhLF, (1.5g to 9g), either for 14 days or in cycles of 14 days. The drug was well tolerated with no drug-related serious adverse events reported.

May 6, 2002

Phase II trial results suggest a strong correlation between clinical response and pharmacological action for GD0039, GlycoDesign's lead anti-cancer drug. The trial, which was conducted at five Canadian centers, included 18 subjects with metastatic renal cancer and 22 subjects with metastatic colorectal cancer resistant to 5-fluorouracil. In 14 trial subjects, the cell-surface carbohydrate structures targeted by GD0039 were highly inhibited. Within this population, four of six renal cancer subjects and three of eight colorectal cancer subjects experienced tumor shrinkage or stable disease.

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