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New Medical Therapies™

Solid Tumors

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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.

April 16, 2012

BIND Biosciences released preliminary results from a phase I trial of BIND-014 for the treatment of advanced or metastatic solid tumor cancers. The ascending dose trial plans to enroll approximately 30 heavily pretreated subjects who will receive escalating intravenous doses of BIND-014. The primary objective of the study is to determine the maximum tolerated dose of BIND-014 and to assess preliminary evidence of antitumor activity. Data are from 17 subjects. Six of the 17 subjects showed preliminary evidence of anti-tumor activity, with one durable confirmed partial response (cervical cancer) and five stabilization of disease (pancreatic, colorectal, bile duct, tonsillar and anal cancer). The subjects have been treated up to a dose of 75 mg/m2 with dose escalation continuing. BIND-014 was well-tolerated to date. Data also showed a highly differentiated pharmacokinetic profile from conventional docetaxel and strong dose linearity across doses.

September 26, 2011

Niiki Pharma issued interim results from a phase I trial of NKP-1339 for metastatic solid tumors resistant to standard therapies. This dose escalation trial has enrolled 24 subjects to date. Of these 24 subjects, six (25%) exhibited anti-tumor activity, demonstrated by disease stability and/or tumor regression for at least 12 weeks. Of the responding six subjects, one subject with carcinoid tumor had tumor regression and continues on NKP-1339 therapy for more than 70 weeks. The five other subjects have experienced stable disease of up to 24 weeks with NKP-1339 treatment. These subjects had the following tumor types: one gastrinoma non-pNET, one colorectal cancer, two non-small cell lung cancers and one cancer of unknown primary. NKP-1339 treatment has been well tolerated to date with mild manageable side effects. The most common drug-related side effect was grade 1-2 fever and mild flu-like symptoms. The maximum tolerated dose has not been reached.

July 11, 2011

CytRx released interim results from a phase Ib trial of INNO-206, a tumor-targeted doxorubicin conjugate, for solid tumors. Data are from eight subjects with advanced solid tumors who had failed standard therapies. The subjects received one of two INNO-206 dose levels: 165 mg/m2 or 260 mg/m2 doxorubicin equivalents. These doses are 2.75 and 4.33 times higher than the standard dose of doxorubicin. No dose limiting toxicities were reported at doses over four times higher than the standard doxorubicin dose. Side effects were generally mild however one subject experienced grade 3 or 4 neutropenia and thrombocytopenia that resolved without therapy.

May 30, 2011

VBL Therapeutics reported results from an ongoing phase I/II trial of VB-111 for the treatment of advanced solid tumors. Data are from 33 subjects with progressing, advanced solid tumors and no existing curative therapy. The subjects were enrolled across seven single, intravenous dosing cohorts. Primary and secondary endpoints were safety and efficacy 56 days after dosing. On day 56, three of the 14 subjects (21%) in cohorts one to five and nine of the 18 subjects in cohorts six and seven had stable disease. One subject with papillary thyroid carcinoma had a partial response persisting for 18 months post dosing and three subjects, one with neuroendocrine and two with thyroid carcinoma, had a significant decline in tumor-markers. VB-111 was safe and well tolerated.

October 11, 2010

Celldex released positive interim results from a phase I/II trial of CDX-1401, a vaccine under development for NY-ESO-1-expressing malignant solid tumors. This dose escalation trial has enrolled 20 subjects at multiple clinical sites in the United States, including Yale University, Henry Ford Health System and Cornell University. The subjects received three different doses of the vaccine in combination with resiquimod. Of the 20 enrolled subjects, 35% had confirmed NY-ESO-1 expression. Six subjects maintained stable disease and were eligible for multiple cycles of the treatment regimen, including four subjects who received three or more cycles, with stable disease of up to 11.5 months. The treatment was well tolerated and there were no dose-limiting toxicities. Robust anti-NY-ESO-1 immunity was induced with the majority of the subjects developing anti-NY-ESO-1 antibody responses and 39% of the subjects having increases in NY-ESO-1 specific T cell responses, including both CD4 and CD8 responses.

June 28, 2010

Semafore reported positive interim results from an ongoing phase I trial of SF1126 for the treatment of solid tumors. In this dose escalation study subjects were administered SF1126 in 90-minute intravenous infusions twice per week on days one and four of four week cycles. To date 19 of 33 evaluable subjects showed stable disease as best response with a median duration of 13 weeks and a mean duration of about 19 weeks. There were three subjects with stable disease for six months or longer. The maximum tolerated dose was not reached, with the maximum administered dose being 1,110 mg/m2. SF1126 was well tolerated.

August 3, 2009

Ariad reported results from two trials of ridaforolimus for the treatment of breast cancer and solid tumors. The first was a phase II study of ridaforolimus combined with trastuzumab for metastatic breast cancer. This ongoing trial has enrolled 28 subjects with metastatic breast cancer who have become resistant to trastuzumab. The subjects received oral ridaforolimus (40 mg/day, once daily) and trastuzumab at standard doses and intervals. The primary endpoint was objective response rate defined by RECIST criteria in at least 15% of the population. Of 28 refractory patients enrolled thus far, 15 currently remain on study without disease progression. At least five partial responses have been observed to date and the preliminary clinical benefit rate was 35%. The second trial was a phase I trial of ridaforolimus combined with bevacizumab in solid tumors. This study enrolled 17 subjects with metastatic solid tumors who had become resistant to bevacizumab. The subjects received the standard dose of oral ridaforolimus (40 mg/day, qdx5) in combination with each of the two approved bevacizumab dosing regimens (infusions every two or three weeks). Of the 17 enrolled subjects, 5 remain on study without disease progression. To date, the longest duration of stable disease was 10 cycles of therapy in a patient with advanced pancreatic cancer; this patient also had a 13% reduction in tumor size.

February 4, 2008

Bayer and Onyx released positive results from an ongoing phase I/II trial of sorafenib for the treatment of acute myeloid leukemia (AML). This trial enrolled newly relapsed subjects and those newly diagnosed with high-risk disease. The subjects received sorafenib in combination with the standard of care chemotherapy combination for AML, idarubicin and cytosine arabinoside. Results showed that sorafenib targeted the FLT3-ITD mutation, a genetic mutation active in about one third of the subjects with AML. In sixteen evaluable subjects with this mutation, sorafenib reduced the median percentage of leukemia cells circulating in the blood from 81% to 7.5% and in the bone marrow from 75.5% to 34%. In addition, two subjects had circulating leukemia cells, or blasts, drop to zero. Treatment was well tolerated to date and the maximum tolerated dose has not been reached. Based on the results the trial will continue as planned.

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.

Wilex released positive results from a phase I trial of WX-UK1 for the treatment of solid tumors. This dose escalation study enrolled twenty five subjects who received once weekly infusions of WX-UK1 for three weeks at various fixed doses and daily capecitabine (Xeloda) concomitantly for two weeks. This three-week cycle was repeated until disease progression or toxicity, or for a maximum of fifteen treatment cycles. Treatment was safe and well tolerated, with no increase in adverse events and no reported serious adverse events. Pharmacokinetic analysis showed no significant reciprocal drug-drug interactions. WX-UK1 showed dose-linear pharmacokinetic profile over the dose range tested. Preliminary efficacy data revealed prolonged stable disease and partial response in several of the subjects. Based on the results, Wilex plans to continue the development of WX-UK1.

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.

October 29, 2007

Exelixis released positive results from an ongoing phase I trial of XL184 for the treatment of solid tumors. To date, this open-label, dose-finding trial had enrolled 33 subjects with unresectable or malignant advanced solid malignancy or lymphoma in whom alternative therapy does not exist or is ineffective. The subjects received two cycles of XL184, administered as a daily oral dose for 5 consecutive days with a 9-day observation period (0.08-11.52 mg/kg), or dosed daily (175 and 265 mg). Of seven subjects with thyroid cancer, 3 had partial responses, 6 had tumor shrinkage and 1 had non-measurable disease. All seven subjects experienced a rapid decrease in plasma levels of calcitonin and six had a decrease in the tumor marker carcinoembryonic antigen. In addition, one subject with a neuroendocrine tumor had an unconfirmed partial response. Fifteen subjects with various solid malignancies or lymphoma have had stable disease lasting from three months to up to 20 months, including nine with stable disease for more than six months. Preliminary pharmacokinetic analyses of nine dose levels (0.08-11.52 mg/kg) indicate a long half-life of 59 to 136 hours. Treatment has been well tolerated and dose escalation is continuing to determine the maximum tolerated dose. Based on positive results, Exelixis plans to commence phase II trials by the end of 2007.

Human Genome Sciences reported positive results from a phase Ib trial of lexatumumab for the treatment of cancer. This open-label, dose-escalation study enrolled 41 subjects with a variety of solid malignancies. The subjects received HGS-ETR2 (5 mg/kg or 10 mg/kg) administered intravenously, plus a full-dose regimen of chemotherapy (gemcitabine, pemetrexed, doxorubicin or FOLFIRI). Objective responses were reported for two subjects; one with colorectal cancer in the FOLFIRI arm and one with small-cell lung cancer in the doxorubicin arm. Stable disease was observed in 22 of the subjects. The pharmacokinetics of lexatumumab were not affected by the chemotherapeutic agents, nor were the pharmacokinetics of the chemotherapeutic agents affected by lexatumumab. Treatment was determined to be safe and well tolerated. Based on the results, the company plans to advance the development of lexatumumab.

November 20, 2006

Kosan announced positive results from two ongoing phase I trials of KOS-1584 for the treatment of solid tumors. The first trial enrolled 37 subjects who received KOS-1584 via one-hour weekly intravenous infusion, in doses escalating from 0.8 to 25 mg/m2, every three out of four weeks. Treatment was generally well tolerated with low grade toxicities reported. Pharmacokinetic data revealed a half-life of 20-25 hours and a large volume of distribution. Antitumor activity was observed in 17% of the subjects, with one confirmed partial response and four subjects who reached stable disease over four or more cycles of treatment. The second trial enrolled 45 subjects who received KOS-1584 administered as a three-hour intravenous infusion, in doses escalating from 0.8 to 36 mg/m2, every three weeks. Treatment was well tolerated with the most common toxicities mild in nature. Antitumor activity was observed in 29.5% of the subjects, with 12 subjects reaching stable disease after 4 or more cycles of treatment. Both of these trials are ongoing in order to determine the best dose for phase II trials.

June 12, 2006

Ariad Pharmaceuticals announced positive results of a phase II trial of AP23573, for the treatment of soft-tissue and bone sarcomas. Trial data indicated significant improvements in the trial's co-primary endpoints, clinical benefit rate (CBR; combined rate of complete response, partial response and stable disease) and duration of progression-free survival (PFS) for patients with the three most common subclasses of sarcoma. Specifically, CBR was 30% for patients with bone sarcoma; 33% for leiomyosarcoma, and 30% for liposarcomas, compared to a historical baseline of 8%; rate of PFS through 6 months (24%) and median duration of PFS (15 weeks) did not significantly differ between the 3 groups, and was superior to a historical baseline of 7 weeks. Patients with less common "other" sarcomas experienced a 6-month PFS rate comparable to the other sub-groups, though CBR was lower (23%), and below the pre-determined 25% success threshold. This multi-center study enrolled 212 patients with metastatic and/or unresectable disease, who received fixed doses of 12.5 mg AP23573 monotherapy via intravenous infusion in 4-week cycles of 5 days on/9 days off treatment.

Exelixis reported positive results of a phase I trial of XL647, for the treatment of solid tumors. Trial data yielded preliminary evidence of efficacy, with 1 partial response (NSCLC) and 12 cases of stable disease through at least 3.5 months (3 NSCLC, 2 chordoma, 2 adenoid cystic carcinoma, and 1 each adrenocortical carcinoma, colorectal, ovarian, mesothelioma, and head & neck cancer). Maximum tolerated dose was set at 4.68 mg/kg; 2 subjects administered doses higher than this level experienced dose-limiting grade 3 diarrhea. This dose-escalation study enrolled 40 subjects, who were received multiple oral doses of the drug (0.06 mg/kg to 7.0 mg/kg).

GlaxoSmithKline reported positive results of a phase III trial, dubbed EGF100151, of Tykerb, for the treatment of breast cancer. Trial data yielded significant efficacy, significantly extending time to disease progression compared to control therapy (36.9 weeks vs. 19.7 weeks; p=0.00032). Rates of treatment-related adverse events leading to discontinuation were comparable between the Tykerb (14%) and control (11%) regimens. This international, multicenter, open-label study enrolled 392 women with trastuzumab-refractory ErbB2 positive breast cancer, who received either a combination regimen of Tykerb and the approved drug capecitabine, or capecitabine alone. These results were sufficiently positive for the trial's DSMB to recommend early termination of the study in April 2006, so all patients could be transferred to the combination regimen.

ImClone announced positive results of a phase I trial of IMC-1121B, for the treatment of advanced cancers. Maximum tolerated dose had yet to be reached, with anorexia, vomiting, anemia, depression, fatigue and insomnia noted as the most frequent adverse events. These adverse events were noted as potentially distinct from those observed with other compounds designed to disrupt the VEGF system. Preliminary evidence of efficacy was also noted, with 1 partial tumor response and 5 instances of stable disease. This open-label study had enrolled 14 subjects to date, and dose-escalation was ongoing.

Pharmion and MethylGene reported interim results of a pair of phase I trials of MGCD0103, for the treatment of hematological malignancies (leukemias and myelodysplastic syndromes (MDS)), and solid tumors. Both trials were open-label, dose-escalation monotherapy studies, which had enrolled 23 and 28 patients to date, respectively. In the leukemia/MDS study, the maximum tolerated dose was somewhat below 80 mg/m2 thrice weekly, at which dose nausea, vomiting, diarrhea, and/or fatigue were dose-limiting. 3 patients (2 with acute myelogenous leukemia, 1 with MDS) achieved complete bone-marrow response. In the solid tumor trial, maximum tolerated dose had not yet been reached; the most common adverse event to date was Grade 1-3 fatigue. Stable disease was observed in 5 subjects (3 kidney cancer, 1 NSCLC and 1 colon cancer). Based on these results, the company announced plans to initiate a phase I/II trial of the drug in Q2 2006, with phase II trials to follow before year's end.

April 10, 2006

ArQule issued positive results of a phase I trial of ARQ 501, for the treatment of solid tumors, at the AACR Annual Meeting. Results from the study yielded preliminary efficacy, with tumor regression (2 parital responses, 3 minor responses) or disease stabilization (13 subjects) observed in a number of cancer types, including pancreatic, head and neck, ovarian, and colorectal cancers and leiomyosarcoma. Safety data were also generally positive: serious adverse events included hyperbilirubinemia and dose-limiting hemolytic anemia, but these were transient and clinically manageable. This open-label study enrolled a total of 64 subjects, who received dose-ranging regimens of the drug (10 mg/m2 to 660 mg/m2) via one- or three-hour infusion.

Maxim, through their merger partner EpiCept, announced positive results of a phase III trial of Ceplene for the treatment of AML in the journal Blood. This randomized study enrolled 320 subjects in 11 countries, who received Ceplene plus low dose interleukin-2 or current standard of care (no treatment). Results from the study achieved significance in the primary efficacy endpoint, extending leukemia-free survival at >3 years of follow-up (p=0.0096 in intent-to-treat analysis); the majority of responses were in patients experiencing their first complete remissions (n=261), among whom 3-year leukemia free survival rates were 40% vs. 26% (p=0.01). No treatment-related mortality was observed, and rate of serious adverse events for Ceplene therapy was comparable to the control group.

Sunesis announced positive results of a phase I trial of SNS-595, their napthyridine analog under investigation for the treatment of solid tumors, at the Annual Meeting of the American Association for Cancer Research (AACR). Trial data yielded preliminary evidence of clinical activity, with 28.6% of subjects (n=6/21) achieving sustained disease control through at least 16 weeks; one partial tumor response was noted at the maximum tolerated dose. The drug was shown to be well tolerated: one case of dose-limiting neutropenia was observed, while other adverse events were generally mild. This open-label dose-escalation study enrolled 21 patients with advanced solid tumors. These data were seen to support ongoing phase I (acute leukemias) and phase II (non-small cell and small cell lung cancers) trials of the drug.

March 6, 2006

Algeta announced positive results of a phase II study, dubbed (BC1-02), of Alpharadin (radium-223), for the treatment of bone metastases related to hormone-refractory prostate cancer (HRPC) at the ASCO Prostate Cancer Symposium. The trial met its primary efficacy endpoint, with Alpharadin significantly decreasing bone-alkaline phosphatase, a bone-turnover biomarker compared to placebo at 4 months (p<0.001). Efficacy was also noted in reducing secondary markers of bone turnover, including the S-PINP bone formation marker and the S-CTX-I and S-ICTP bone resorption markers. Prostate-specific antigen levels were also reduced. This double-blind placebo-controlled study enrolled 64 patients with bone metastases due to HRPC at 11 sites in Norway, Sweden and the UK. Additional 12 month data, including figures on long-term safety and survival, were expected in the second half of 2006.

Alizyme has issued positive result of a phase IIa trial of ATL-104, for the treatment of oral mucositis related to chemotherapy. Results from the study indicated that all 3 doses of the drug reduced mean duration of WHO Grade 2-4 mucositis (3.2 to 4.5 days) relative to placebo (5.9 days). Subgroup analysis indicated that serious Grade 3-4 mucositis was also reduced for all 3 doses (2.4 to 3.1 days, vs. 5.4 days). Secondary efficacy data were also positive, including efficacy on the WCCNR scale, reduced incidence of oral ulceration and pain, and duration of time patients were unable to take solids by mouth. This randomized, double-blind, multi-center study enrolled 64 patients undergoing chemotherapy across 8 sites in the UK, who received 1 of 3 dose regimens of the drug or placebo prior to autologous peripheral stem cell transplantation.

Spectrum Pharmaceuticals announced positive results of a phase I trial of satraplatin for the treatment of solid tumors at the 2006 ASCO Prostate Cancer Symposium in San Francisco. Trial data yielded a positive overall safety profile, with no significant cardio, renal, liver or neurological toxicities. Overall toxicities, including nausea, vomiting and diarrhea, were mild to moderate in nature, and effectively controlled with prophylactic anti-emetic therapy. Preliminary efficacy data yielded a 1 partial response and 2 cases of stable disease. Administration of the drug with a high-fat meal was shown to reduce peak plasma drug concentration by approximately 20%. The study enrolled 17 heavily pretreated patients with advanced solid tumors.

November 28, 2005

Ariad Pharmaceuticals issued positive interim results of a phase Ib trial of an orally administered formulation of AP12573, their investigational mTOR inhibitor for the treatment of solid tumors. Data from the first 45 patients yielded a positive oral-dose tolerability profile across three daily dosing regimens: continuous daily dosing; dosing for 3 of every 4 weeks; and dosing for 4 of every 7 days. Maximum tolerated dose was reached in each of the first two regimens (10 mg and 15 mg daily, respectively), with oral mucositis noted as the dose limiting toxicity for each indication; dose-escalation was ongoing in the third group, and had reached doses of 40 mg daily on treatment days. This open-label dose- escalation had enrolled 58 subjects to date. The company announced plans to initiate investigation of additional regimens of the drug.

CuraGen and TopoTarget announced positive interim results of a phase I trial of PDX101, their histone deacetylase inhibitor for the treatment of solid tumors. Pharmacokinetic data yielded a dose-related absorption profile across trial regimens, and an elimination half-life of approximately 1 hour. Dose-proportional bioactivity was noted in histone hyperacetylation, which lasted 6-24 hours. Oral bioavailability was approximately 33%. No serious hematological toxicities were noted. This ongoing open-label dose-escalation study enrolled 42 patients with advanced refractory solid tumors, who received intravenous or orally available formulations PXD101 monotherapy. Based on these data, the company selected a dose of 1000 mg/m2 for use in upcoming phase II trials. Additional results of the study were to be presented at the annual meeting of the American Society of Hematology in December.

Point Therapeutics issued positive results of a phase II trial of talabostat for the treatment of non-small cell lung cancer (NSCLC). The drug produced an objective response rate (defined as a reduction in tumor size of at least 50%) of 11.9% (n=5/42); this included 3 partial responses and 2 ongoing complete responses (since March and April 2005). Median progression-free survival was 4.2 months, and median overall survival was 8.4 months; among the 31 patients enrolled in the study for at least a year, one-year survival rate was 48%. This open-label study enrolled 42 evaluable patient with relapsed or refractory NSCLC (64% second line, 36% third line or later; 75% failing a prior platinum/taxane regimen), who received talabostat in combination with docetaxel.

September 12, 2005

GlycoGenesys has reported positive interim results of a phase I trial of their investigational their galectin-3-targeted drug GCS-100, for the treatment of solid tumors. The trial met its primary objective of establishing the maximum tolerated dose for the treatment regimen. Preliminary safety data from the first 17 patients yielded a positive overall tolerability profile, with a dose limiting toxicity of a steroid-manageable rash. The drug also demonstrated a linear pharmacokinetic profile, and clinically relevant plasma concentrations were safely achieved. Preliminary efficacy data yielded stable disease in 11 of 14 evaluable subjects, lasting from 1.5 to more than 8 months; 3 of the stable patients were non- responsive to previous therapies. This ongoing open-label study had enrolled 22 patients to date at 2 sites in the US, who received escalating doses of the drug on a 5-days-on, 2-weeks-off treatment schedule. Based on these results, a phase I/II trial of the drug for the treatment of chronic lymphocytic leukemia is scheduled to begin by October 2005.

OncoGenex reported positive results of a phase I trial of OGX-011, for the treatment of prostate cancer, in the Journal of the National Cancer Institute. The trial met its primary pharmacokinetic endpoint, establishing the optimum dose for future phase II trials (640 mg). Success in secondary endpoints was also noted, including a significant and predictable increase in peak plasma concentration (p<0.001), significantly dose-related peak drug concentrations in prostate tissue (p<0.001), and a significant reduction expression of the drugs target protein clusterin, by more than 90% (p=0.008). Clusterin reduction at the optimum dose lead to a significant increase in apoptotic tumor cell death (21.2%, p<0.001). The study enrolled patients through the National Cancer Institute of Canada Clinical Trials Group, who received dose-ranging infusions of the drug prior to radical prostatectomy.

July 18, 2005

Aphton reported positive results of a phase I trial of their anti-Lewis Y tumor-associated antigen monoclonal antibody IGN311, for the treatment of solid tumors. Data yielded a positive safety profile, with no adverse events reported for the low and middle dose regimens and 1 event (nausea & vomiting) noted in the high dose regimen. Pharmacokinetic results indicated a mean serum half-life of at least 20 days. Preliminary efficacy results demonstrated a reduction in the number of circulating Lewis-Y-positive tumor cells in those patients with detectable levels of these cells prior to treatment. This open-label dose- escalation study enrolled 12 subjects with Lewis Y positive epithelial tumors (breast, colorectal, gastric and pancreatic). Subjects received one of three doses of the drug (50 mg, n=3; 100 mg, n=3; or 200 mg, n=6) on days 1 and 15 of the study period. The company announced plans to initiate additional trials of the drug in the near future.

Genentech and OSI Pharmaceuticals announced that results of a phase III trial of their approved EGFR inhibitor Tarceva (erlotinib), for the treatment of non-small cell lung cancer (NSCLC), have been published in the New England Journal of Medicine. Results from the study indicated that Tarceva produced a 8.9% overall response rate, compared to <1% for placebo (p<0.001); median response durations were 7.9 months and 3.9 months, respectively. Progression free survival was also improved to 2.2 months, compared to 1.8 months for placebo (p<0.001), and overall survival, the primary endpoint, was 6.7 months, vs. 4.7 months for placebo, a reduction in mortality risk of 30% (p<0.001). Finally, 1 year survival rates also improved (31% vs. 22%, respectively). This double- blind, placebo-controlled study enrolled 731 NSCLC patients who had failed 1 or 2 prior chemotherapy regimens across 86 sites in 17 countries. Subjects were randomized 2:1 to receive 150mg Tarceva or placebo daily.

January 31, 2005

Genentech issued positive results of a phase IIIb study of Avastin (bevacizumab) in combination with FOLFOX4 chemotherapy, for the second-line treatment of metastatic colorectal cancer. Preliminary results met their primary endpoint, producing a significant reduction in risk of death (hazard ratio=0.74) and a 17% improvement in median survival time (2.5 months vs. 10.7 months), vs. subjects receiving FOLFOX4 alone. The safety and tolerability profile for the combination therapy was consistent with those observed for both drugs alone; the most frequent serious adverse events were bleeding (3/286) and thrombosis (13/286), and the most frequent adverse events were hypertension (17/286) and (44/286) sensory neuropathy. This randomized, controlled, multicenter trial enrolled 829 patients with advanced colorectal cancer refractory to 5-FU-based and irinotecan therapies.

OSI Pharmaceuticals and Genentech reported results of a phase III trial of their approved EGFR inhibitor Tarceva (erlotinib) for the treatment of advanced pancreatic cancer. The study found that adding Tarceva to a standard regimen of gemcitabine chemotherapy significantly improved survival, with 24% of patients receiving the drug combination reaching 1 year survival, vs. 17% for gemcitabine plus placebo (hazard ratio = 0.81, p=0.025), with median survival rates of 6.4 and 5.9 months, respectively. Progression-free survival was significantly improved (hazard ratio=0.76, p=0.003), although significant improvement was noted in tumor response rate (9% vs. 8%, p>0.05). No unexpected safety issues were raised, with no indication of drug-drug interactions between Tarceva and gemcitabine leading to new adverse events. This double-blind, placebo-controlled multi-center study randomized a total of 569 subjects to receive gemcitabine plus either 100 mg/day Tarceva or placebo (n=521), or 150 mg/day Tarceva or placebo (n=48), until disease progression. The study had sites in the United States, Asia, Canada, Europe, Australia and South America, and was headed by the National Cancer Institute of Canada Clinical Trials Group.

Pro-Pharmaceuticals announced preliminary results from a phase I trial of Davanat, their polysaccharide chemotherapy delivery vehicle, for the treatment of solid tumors. Study data indicated that the drug, both alone and in combination 5-FU chemotherapy, met the primary safety endpoints, with no dose limiting toxicity attributable to Davanat observed. Furthermore, preliminary evidence of efficacy with Davanat/5-FU was observed, with 45% of subjects achieving stable disease. This ongoing open-label study has completed enrollment with 40 subjects with advanced solid tumors not amenable to surgery, radiation, or chemotherapy. Subjects received escalating doses of Davanat alone and in combination with 5-FU chemotherapy over 2 28-day treatment cycles.

November 29, 2004

Alteris Therapeutics has announced positive results of a phase I clinical trial of their EGFRvIII peptide therapeutic vaccine, for the treatment of malignant glioma. Results from the trial met their primary safety and tolerability endpoints, with no serious adverse events reported and a favorable tolerability profile. Furthermore, the drug demonstrated significant preliminary evidence of efficacy: 2 patients experienced near-complete remission after vaccination, more than 25% of subjects experienced stable disease state during the study, median overall time to disease progression was 314 days, compared to a historical baseline of I24 days, and median survival time was over 596 days, or about 20 months, compared to a historical baseline of 11-13 months. This open-label safety and efficacy trial enrolled a total of 16 patients with malignant glioma at 1 US site, who received a total of three doses of the trial once every two weeks.

Hybridon has issued positive interim results of a phase I trial of IMOxine, their investigational second-generation immunomodulatory oligonucleotide for the treatment of solid tumors. Results from the 19 subjects completing safety evaluations met primary safety and tolerability endpoints, with no dose-limiting toxicity, a tolerability profile consistent with immune system stimulation, and a manageable adverse event profile including transient hypoxia/dyspnea (n=1), abdominal pain with nausea/vomiting (n=1), and anemia requiring transfusion (n=2). There were 4 early withdrawals, all due to disease progression. Furthermore, results from the 17 subjects completing preliminary efficacy evaluations indicated that the drug produced stable disease state in 53% of patients (n=9) after 8 weeks of treatment, and 1 of these subjects maintained this state into the 11th month of treatment. This open-label, open-duration safety and immunpharmacology study enrolled 23 patients with assorted refractory solid tumors at 1 US site. Subjects received IMOxine via weekly subcutaneous injection at one of 5 dosing regimens (0.04, 0.16, 0.32, 0.48, or 0.64 mg/kg).

Pharmacyclics announced the combined results of two phase I trials of Xcytrin (motexafin gadolinium) in combination with cranial irradiation for the treatment of glioblastoma multiforme (GBM). Data from both trials indicated that the duration-ranging regimens met primary safety and tolerability endpoints, with no drug related interruptions of radiation therapy and a manageable adverse event profile which included numbness, tingling and rash of fingertips, nausea and mild diarrhea, and reversible hepatic chemistry abnormalities. Preliminary evidence indicates that the drug promoted improvements in survival. Specifically, patients receiving a cumulative dose >60 mg/kg of Xcytrin experienced a median survival time of 11.5 months, with 82% alive at 6 months and 46% at 12. Patients a cumulative dose <60mg/kg experienced median survival of 16.4 months, with 93% and 78% alive at 6 and 12 months. Overall median survival for the entire group of patients was 14.7 months, with 91% and 69% alive at 6 and 12 months. Both trials were open-label, cumulative-dose-escalation studies (40-117 mg/kg), which enrolled a combined total of 55 subjects with treatment-naïve GBM.

November 15, 2004

Adherex Technologies reported updated results from a phase I safety and tolerability trial of Exherin, their investigational tumor-specific blood vessel destabilizing agent for the treatment of refractory, incurable solid tumors. Preliminary data indicate that the drug was safe and well tolerated across dose-ranging regimens of the drug, with mild fatigue, nausea, and transient dysgeusia noted most often. Maximum tolerated dose (MTD) has not been reached. In addition, preliminary evidence of efficacy was observed, with one partial response (>50% reduction in tumor size), one mixed response (<50% reduction in tumor size), and one secondary response (reduction in hormone hyper-secretion and evidence of necrosis in a patient with adrenal tumor). This open-label safety, tolerability, pharmacokinetic and MTD study has to date enrolled 29 subjects with incurable solid tumors, who received 45 treatment cycles of one of seven doses of the drug (50 mg/m2 to 840 mg/m2). Adherix announced that they have increased their patient enrollment rate with the inclusion of new investigative sites, and have additional plans to initiate an optimal-dose finding phase Ib/II trial before the end of 2004.

Spectrum Pharmaceuticals presented positive data from an ongoing phase II safety and efficacy trial of EOquin (apaziquone) for the treatment of bladder cancer at the Chemotherapy Foundation Symposium in New York. Interim data indicate that the drug demonstrated significant efficacy in treating recurrent refractory superficial bladder cancer, with 64% of the patients completing 6 weekly treatments (18 of 28) exhibiting complete disappearance of tumors. In addition, the drug has exhibited a positive safety profile, with low observed systemic absorption, no systemic toxicity, and only one case of localized toxicity (chemical cystitis). This ongoing, multi-center, open-label study is investigating the safety and efficacy of weekly intra-bladder administrations of EOquin for 6 weeks. It was designed to enroll up to 45 subjects with recurrent refractory superficial bladder cancer; 36 (28 evaluable) have been enrolled to date, and Spectrum announced that they expected enrollment to be completed by the end of 2004.

Vical Incorporated announced safety and efficacy results from a phase II trial of Allovectin-7, their gene therapy product under investigation for the treatment of metastatic melanoma, at the Annual Meeting of the International Society for Biological Therapy of Cancer. Trial data demonstrated that the drug produced clinical responses in 11.8% of subjects (n=15), including four complete responses and 11 partial responses. Furthermore, the company observed a median response duration of 12.7 months, and a median survival duration of 21.3 months. This open-label study enrolled a total of 133 patients, 127 of whom received the highest dose regimen of the drug (2 mg), and were evaluated for efficacy. Vical announced that it intended to use this data in support of a Special Protocol Assessment with the FDA, which would permit the initiation of an approval-enabling phase III trial, before the end of Q4 2004.

October 4, 2004

Ariad Pharmaceuticals reported interim results of a pair of phase I single-agent study of AP23573, their mTOR inhibitor for the treatment of solid tumors. Trial results showed to drug to be efficacious in treating solid tumors, with 49% (24 of 49) of subjects demonstrating a tumor response; this included 9 partial responses (reduction of tumor size by at least 30%), 5 partial responses (reduction of tumor size by 15%-29%), and 14 disease stabilizations. Median response was 5 months, with some responses extending to 18 months. The drug was well tolerated in both trials, with oral mucositis observed as the dose limiting toxicity. The two trials have to date enrolled a total of 49 subjects with mixed solid tumors; 27 subjects in a daily-dosing investigation and 22 subjects on a weekly-dosing regimen. Both trials are ongoing.

Bayer Pharmaceuticals and Onyx Pharmaceuticals reported the results of a phase II single-agent study of BAY43-9006, their RAF kinase/VEGFR inhibitor being investigated for the treatment of advanced hepatocellular carcinoma (HCC), at the 16th meeting of the American Association for Cancer Research – National Cancer Institute – European Organization for Research and Treatment of Cancer in Geneva, Switzerland. Results of the trial indicated that the drug demonstrated significant efficacy, with 43% of subjects demonstrating 4-month stable disease state, 4% of subjects demonstrating a reduction in tumor size of 25% to 50%,and 5% of subjects demonstrating tumor shrinkage of 50% or more. Median survival rate for all subjects was 9.2 months, and median time to progression was 4.2 months. The open label study enrolled a total of 137 treatment-naïve patients with advanced HCC, all of whom received 400 mg. twice daily in continuous 4-week regimens. Based on this data, the companies announced plans to initiate a phase III single-agent trial, as well as a phase II chemotherapy adjuvant trial.

Epimmune Inc. announced positive combined results of two phase I trials of their multi-epitope cancer vaccine candidate EP-2101, for the treatment of non-small cell lung cancer (NSCLC) and colorectal cancer. Preliminary efficacy data have indicated that the vaccine is strongly immunogenic, with 93% of subjects demonstrating immunological response to at least 1 of the 9 antigenic vaccine components, 53% of subjects demonstrating response to 5 of the 9, and a median response to 4 of the 9. The vaccine was safe and well tolerated. The trials enrolled a total of 24 subjects with stage IIB/IIIA NSCLC or stage III colorectal cancer, all of whom received a total of 6 treatments with the vaccine, once every three weeks for 18 weeks. Following the results of these two investigations, Epimmune announced plans for the initiation of a phase II trial in NSCLC, to be initiated by the end of 2005.

January 5, 2004

Genmab reported positive interim results from two phase II trials investigating HuMax-CD4 for the treatment of cutaneous T-cell lymphoma (CTCL). Results showed 55% of the early stage and 38% of the advanced stage subjects achieved at least a partial response, using the Physician's Global Assessment (PGA) scale. The PGA is a comparison of baseline conditions that grades all cancerous lesions from 0 to 6. Data showed that 9% of the early stage and 23% of the advanced stage patients achieved a minor response. In addition, pruritus was improved in 82% of early stage patients and 69% of advanced stage patients. The study enrolled 11 early stage and 13 advanced stage subjects with CTCL.

Introgen reported data from a phase I clinical trial indicating that INGN 241, an MDA-7 gene therapeutic, was well tolerated and was clinically active in subjects with solid tumors. Results showed that the MDA-7 protein was detectable 4 cm away from the injection site. Intratumoral injection of INGN 241 produced protein both in local and diffusible forms. This observation was correlated with apoptosis at the external edge of the tumor that was injected. Results were reported at the 12th Annual International Conference on Gene Therapy of Cancer in San Diego. INGN 241 is currently in phase II clinical trials for the treatment of solid tumors.

Millennium Pharmaceuticals announced positive preliminary results from a phase I/II, investigator-initiated trial with Velcade (bortezomib) in combination with thalidomide with dexamethasone for the treatment of advanced stage multiple myeloma. Of the 56 subjects who are currently enrolled in the trial, 96% received prior autotransplant and 81% received prior thalidomide. Investigators reported that responses were observed in subjects who had previously received thalidomide treatment, and more than 20% of subjects achieved a complete or near complete response. Adverse events included gastrointestinal events, fatigue, peripheral neuropathy and hematologic toxicities. Results were reported at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.

October 27, 2003

Astrazeneca reported final results from a pivotal phase II trial investigating Iressa (gefitinib), an approved drug for the treatment of non-small cell lung cancer. Results showed that 12% of subjects who received Iressa (250 mg),once daily, demonstrated at least a 50% reduction in tumor size. Further analysis showed a tumor response rate of 13.6% at the recommended dose of 250 mg and 10.6% overall for both doses tested. The median duration of response was 7 months. The double-blind, randomized study enrolled 216 subjects who had previously received two or more types of chemotherapy. Iressa is approved in the U.S. for use as monotherapy for the treatment of advanced non-small cell lung cancer after failure of both platinum-based and docetaxel chemotherapy. Results were reported in October 2003 in The Journal of the American Medical Association.

GlycoGenesys reported positive results from a phase I trial investigating GSC-100, a Galectin-3 targeting agent for the treatment of various cancers. Results showed that five (41.7%) subjects achieved stable disease for at least three months. One subject still remains on GCS-100 after 18 months of treatment and has achieved a partial response. GCS-100 was well tolerated with no dose-limiting toxicity observed. A maximally tolerated dose was not reached at dose levels up to 80 mg/m2. The open-label, dose escalation study enrolled 12 subjects and was designed to test the drug on subjects with unresectable, relapsed, or refractory advanced solid tumors for which there is no curative therapy. GCS-100 was administered intravenously, twice weekly, at doses of 30, 42.5, 60 or 80 mg/m2 for up to six, four-week treatment cycles, or six months.

October 13, 2003

American Pharmaceutical Partners and American BioScience reported positive results from a phase III trial investigating Abraxane (ABI-007), a nanoparticle albumin-bound paclitaxel for the treatment of metastatic breast cancer. Results demonstrated that Abraxane achieved higher anti-tumor activity and less toxicity than Taxol. Data showed a higher tumor response rate and a longer time to tumor progression in subjects receiving Abraxane. In addition, a secondary analysis showed the target lesion response rate was found to be significantly higher with Abraxane compared to Taxol. Both treatment regimens were well tolerated. The pivotal, randomized, controlled trial study enrolled 460 subjects and was designed to compare the safety and efficacy of Abraxane to Taxol, administered every three weeks. The dose of paclitaxel (260 mg/m2) was approximately 50% higher than that in the Taxol arm (175 mg/m2).

Hybridon reported positive results from a phase I trial investigating GEM 231, an antisense oligonucleotide for the treatment of solid tumors. Results showed low-grade fatigue in 57% of subjects that was cumulative over 4-6 weeks of repeated 5-day infusions and that rapidly reversed at the end of treatment. In addition, dose-related, reversible increases in serum transaminases and activated partial thromboplastin times were observed. The study enrolled 14 subjects who received escalating doses of GEM 231 in continuous intravenous infusion at 80 to 180 mg/m2/day. Results were reported in the September 15th issue of Clinical Cancer Research.

Procyon Biopharma reported positive interim results from a phase IIa trial investigating PCK3145, a natural prostate secretory derived protein for the treatment of prostate cancer. Results showed that two out of the four subjects in the first cohort showed a decline in PSA levels following treatment with PCK3145. Two subjects in the second cohort also showed an initial response in PSA reduction. Data also showed that four subjects who had plasma Matrix Metalloproteinase-9 (MMP-9) levels over 100 ug/L before treatment had reductions ranging from 34% to 90% after two cycles of treatment. The study showed no drug-related adverse effects. Results were reported at BioContact, Quebec City, Canada.

September 29, 2003

AEterna Laboratories reported negative results from a phase III trial investigating Neovastat, an antiangiogenic compound for the treatment of renal cell carcinoma. Results showed that the study did not meet its primary endpoint of improving overall median survival time. The overall median survival time for the Neovastat group was 12.4 months compared to 12.3 months for the placebo group. Significant survival advantages were observed in a subgroup of subjects with clear cell histology and only a single metastatic site. The randomized, double-blind, placebo-controlled study enrolled 305 subjects and was conducted at 50 sites in Canada, the U.S. and Europe. It was designed to evaluate prolonged survival of subjects with progressive metastatic renal cell carcinoma, refractory to immunotherapy.

Kosan Biosciences reported positive results from a second phase I trial of KOS-862 (Epothilone D), a polyketide tumor cell inhibitor for the treatment of solid tumors. Results showed that a dose of 100mg/m2 weekly for three out of four weeks was well tolerated and was associated with mild to moderate toxicity. Data demonstrated preliminary evidence of anti-tumor activity, including significant tumor shrinkage in two subjects with large cell and mediastinal B-cell lymphoma. In addition, results showed stable disease for three months or longer in renal, ovarian, non-small cell lung cancer, cholangiocarcinoma and Hodgkin's lymphoma. The study enrolled 10 subjects and was designed to determine the maximum tolerated dose, toxicity profile, pharmacokinetics and pharmacodynamics of intravenous KOS-862. Results were reported at the ECCO 12 European Cancer Conference in Copenhagen.

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.

Point therapeutics reported positive results from a phase I trial investigating PT-100, a cytokine and chemokine stimulator for the treatment of chemotherapy-induced neutropenia. Results showed a two-day reduction in the median days of severe neutropenia observed in a group of seven subjects who received the 800mcg dose from the second to the eighth day following chemotherapy. A comparison of the median absolute neutrophil counts demonstrated approximately a 60 % reduction in the duration and degree of severe neutropenia in Cycle 2 compared with Cycle 1. The study compared the duration of severe neutropenia in cycle 1 of chemotherapy, when subjects did not receive PT-100, with the duration in cycle 2, when PT-100 was administered. The trial was designed to study the safety of PT-100 in cancer patients receiving chemotherapy and to measure blood levels of neutrophils and important biological mediators of hematopoiesis, such as G-CSF and IL-6.

This information does not represent a Lupus Research Institute endorsement of any listed study. It is merely a notice that the study is available. If you are presently under the care of a physician for lupus or other conditions, you should not disrupt your current program without discussing it with your doctor(s). Do not contact the Lupus Research Institute for information on these studies. Only contact the listed numbers. The Lupus Research Institute does not have any jurisdiction over or further involvement with these studies, other than to make people aware that they are being conducted.