Malignant Melanoma

July 10, 2017

Bristol-Myers Squibb announced promising interim data from its phase III clinical trial of Opdivo 3mg/kg compared to 10mg/kg Yervoy in melanoma. In patients with stage IIIb/c or stage IV melanoma who are at high risk of recurrence after complete surgical resection, Opdivo met its primary endpoint at the planned interim analysis. The endpoint was superior recurrence-free survival (RFS). “These topline results support the potential promise of Opdivo as a treatment option for patients with high-risk surgically resected melanoma,” Vicki Goodman, BMS’ development lead for Melanoma and Genitourinary Cancer, said in a statement. “There remains an unmet need for additional options as the majority of stage III and resected stage IV high-risk melanoma patients experience disease recurrence after surgery. ” The trial is CheckMate-238, which involves 906 patients receiving either Opdivo or Yervoy. The company’s statement did not release any data, but plans to present it at a future medical conference.

November 21, 2016

Pierre Fabre reported results from the pivotal phase III COLUMBUS trial of binimetinib plus encorafenib (bini/enco) treatment in BRAF-mutant melanoma patients The COLUMBUS trial (NCT01909453) is a two-part, international, randomized, open label study evaluating the efficacy and safety of the combination of binimetinib plus encorafenib to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the study. Patients were randomized into two parts. In Part 1, 577 patients were randomized 1:1:1 to receive bini/enco of 45mg binimetinib plus 450mg encorafenib, 300mg encorafenib alone or 960mg vemurafenib alone. In Part 2, 344 patients were randomized 3:1 to receive 45mg binimetinib plus 300mg encorafenib or 300mg encorafenib alone. Part 2 is designed to provide additional data to help evaluate the contribution of binimetinib to the combination of bini/enco. While formal statistical analysis of Part 2 is only planned if both the comparison of PFS between bini/enco versus vemurafenib and bini/enco versus encorafenib achieve statistical significance in Part 1, data from Part 2 are anticipated in mid-2017 and will be provided to global health authorities as part of planned regulatory submissions in 2017. In the analysis of the primary endpoint, the median PFS (mPFS) for patients treated with the combination of bini/enco was 14.9 months versus 7.3 months for patients treated with vemurafenib; hazard ratio (HR) 0.54, (95% CI 0.41-0.71, p<0.001). The Quality of Life (QoL) measures (EORTC Quality of Life Questionnaire Core 30 and Functional Assessment of Cancer Therapy Melanoma Scale Score) were consistent between two scales and showed an advantage in terms of maintaining quality of life for patients receiving bini/enco compared to patients treated with either encorafenib or vemurafenib single agent therapy.

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.

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.

December 8, 2014

Bristol-Myers Squibb has released results of a phase III trial comparing Opdivo to the chemotherapy dacarbazine (DTIC) in patients with treatment naïve BRAF wild-type advanced melanoma. The double-blind study enrolled 418 patients who were randomized to receive either Opdivo 3mg/kg every two weeks (n=210) or DTIC 1000mg/m2 every three weeks (n=208). The one-year survival rate was 73% for Opdivo (95% CI = 66-79) v. 42% for DTIC (95% CI = 33-51). There was a 58% decrease in the risk of death for patients treated with Opdivo (Hazard Ratio for death [HR]: 0.42; 99.79% CI = 0.25-0.73; P<0.0001). Median PFS was 5.1 months and 2.2 months, respectively (HR: 0.43; 95% CI = 0.34–0.56; P < 0.0001). ORR also was significantly higher for Opdivo than DTIC (40% v. 14%, p<0.0001). Complete responses were observed in 7.6% of Opdivo-treated patients v. 1% for DTIC.

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.

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.

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 10, 2008

CuraGen issued positive preliminary results from a phase II trial of CR011-vcMMAE for the treatment of melanoma. This open label, multi-center study enrolled 36 subjects with Stage III or Stage IV melanoma. The subjects received CR011-vcMMAE 1.88 mg/kg administered intravenously once every three weeks. At this time, 31 subjects were evaluable for efficacy and 18 subjects were continuing to receive ongoing treatment in the study. The median overall progression-free survival (PFS) to date was 4.5 months. RECIST-defined partial responses were reported in three subjects, two ongoing, and an unconfirmed partial response in one subject. Stable disease was observed in 19 subjects 14 ongoing, with tumor shrinkage observed in 12 of these subjects. Treatment was well tolerated. Additional phase I and II trials of CRO11-vcMMAE are currently underway.

December 11, 2006

Bayer and Onyx announced negative results from a phase III trial of Nexavar, in combination with carboplatin and paclitaxel, for the treatment of melanoma. This double-blind, randomized, placebo-controlled trial enrolled 270 subjects who received Nexavar or placebo in combination with a standard dosing schedule (21-day cycles) of carboplatin and paclitaxel. The primary endpoint, improvement in progression free survival, was not met with the treatment effect comparable in each arm. Bayer and Onyx plan to continue the development of Nexavar for the potential treatment of various other forms of cancer.

Immunomedics released positive results from a phase II trial of epratuzumab, in combination with rituximab and combined cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (ER-CHOP), for the treatment of diffuse large B-cell lymphoma (DLBCL). This trial enrolled 15 subjects with previously untreated DLBCL who received epratuzumab at 360 mg/m2, followed by rituximab at 375 mg/m2, and a standard dose of CHOP every 3 weeks for 6 to 8 cycles. Treatment was generally well tolerated, although grade 3 or 4 neutropenia observed in 93% of the subjects, or in 28 of 92 cycles (30%), only three subjects developed grade 3 or more infection or fever. Efficacy results revealed that 87% of the subjects responded, including 10 complete responses (67%) and 3 partial responses (20%). At a median follow-up of 30 months, 13 of 15 subjects remained alive. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 93% and 100%, respectively, and the 2-year PFS and OS rates were 86% and 86%, respectively. An additional phase II trial using ER-CHOP is currently underway.

September 25, 2006

AmpliMed released positive interim results from a phase I/II trial of Amplimexon in combination with the drug dacarbazine (DTIC) for the treatment of malignant melanoma. This trial enrolled 69 subjects with stage III and IV melanoma who had not received prior chemotherapy treatment. Subjects received Amplimexon intravenously for 30 minutes followed by an infusion of dacarbazine for 30 minutes, for five consecutive days every three weeks. The phase I portion of the study was designed to assess the safety of this combination treatment and to determine the maximum tolerated dose. The phase II portion was designed to determine the efficacy of the drug at the maximum tolerated dose. Results from phase I showed the combination to be safe and determined the MTD for phase II, with the most common adverse events mild in nature. At this time 32 out of a target 45 subjects had been enrolled in the phase II portion.

BioAlliance reported positive results from a phase I/II trial of doxorubicin Transdrug for the treatment of liver cancer. This trial enrolled 20 subjects who received at least one intra-arterial hepatic injection of doxorubicin Transdrug, at varied doses, in order to determine the maximum tolerated dose for future trials. Efficacy results from the subgroup receiving 30mg/m2 revealed this to be the most promising dose. Disease control was observed in 12 out of 20 (60%) of the subjects, with five partial responses and seven stabilizations. Phase II/III trials are expected to begin shortly.

SciClone and Sigma-Tau announced positive interim results from a phase II trial of Zadaxin for the treatment of stage IV malignant melanoma. Results are from 463 of the 485 enrolled subjects who received Zadaxane combined with standard dacarbazine chemotherapy (DTIC), with or without interferon alpha. Of the 99 subjects treated with 3.2 mg of Zadaxin/ DTIC combination treatment, 12.1% achieved an overall response versus a 5.3% response for the 95 patients in the control arm. Of the 97 subjects treated with 3.2 mg of Zadaxin/DTIC combination therapy and low-dose interferon alpha, 10.3% showed an overall response; and of the 97 subjects receiving 1.6 mg of Zadaxin/DTIC and low-dose interferon alpha, 7.2% showed an overall response. Final results are expected by the end of 2006 with phase III trials planned for early 2007.

March 14, 2005

Adventrx Pharmaceuticals has reported preliminary results of a phase II trial of CoFactor, in combination with 5-fluorouracil, for the treatment of metastatic colorectal carcinoma. Trial results met their primary efficacy endpoint of enhancing response rate, defined as a reduction in tumor size of at least 50%. Additional data, evaluating safety, time-to-tumor-progression and overall survival, were still being collected. This ongoing open-label, single arm, multi-center trial enrolled 48 patients with surgically-unresectable metastatic disease. Treatment of additional patients and data collection are ongoing, and the company plans to present additional data from this study at the 2005 Annual Meeting of the American Society of Clinical Oncology in May.

Medarex and Bristol-Myers Squibb have announced the results of a phase I/II trial of their investigational fully human anti-CTLA-4 antibody MDX-010 for the treatment of melanoma. Study data yielded evidence of efficacy, with 8 of the 36 patients experiencing objective response, including 3 complete responses and 5 partial responses. All three complete responses are ongoing, with 2 through 12 months and 1 through 16 months; partial responses ranged from 7 months to an ongoing response of 19 months. 5 patients experienced serious adverse events, including colitis, uveitis, pancreatitis, arthritis and laryngospasm. This open-label, dose-ranging study enrolled 36 patients with metastatic disease, who were randomized into 1 of 4 3-patient dosing cohorts (0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg and 2.0 mg/kg) or a high dose cohort (3.0 mg/kg; n=24); all patients received MDX-010 treatment once every three weeks, in addition to a high-dose regimen of IL-2.

February 22, 2005

Aphton announced negative results of a phase III study of Insegia (G17DT immunogen) in combination with gemcitabine chemotherapy, for the treatment of pancreatic cancer. Trial data failed to meet their primary efficacy endpoint, with no improvements in overall survival noted versus gemcitabine alone. Survival benefit was noted among the subset of patients who demonstrated antibody response, compared to both the gemcitabine monotherapy arm and those subjects receiving Insegia not demonstrating antibody response. No significant difference in the incidence of adverse events was noted. This randomized study enrolled 383 patients with treatment-naïve pancreatic cancer, who received either combination therapy with Insegia and gemcitabine or gemcitabine alone. The company announced that it hoped to use these results in the design of future trials, and in support of a planned phase III Insegia monotherapy trial in chemotherapy intolerant patients.

Dendreon announced positive results of a phase III study of Provenge (APC-8015), their investigational immunotherapy for the treatment of prostate cancer. Patients receiving the drug experienced a significant 4.5-month improvement in median survival time, vs. placebo (25.9 months vs. 21.4 months, p=0.01). This marks the largest median improvement in survival time in this patient population for any therapy. Efficacy was also noted in promoting survival through 36 months, with 34% of Provenge patients reaching this mark vs. 11% for placebo (p=0.0046). This double-blind, placebo-controlled trial randomized 127 men with asymptomatic, metastatic androgen independent prostate cancer to receive 3 infusions of Provenge or placebo over 4 weeks.

Point Therapeutics reported positive interim results from a phase II trial of talabostat (PT-100), their dipeptidyl peptidase inhibitor for the treatment of metastatic melanoma. Data collected from the first 10 patients yielded preliminary evidence of efficacy, with 1 patient who had previously failed treatment with IL-2 experiencing a partial tumor response (reduction in tumor size of at least 30%). Achievement of this milestone allows the continued accrual of patients. This open-label, single arm study was designed to enroll a total of 30 patients with metastatic melanoma, who were to receive up to 6 cycles of talabostat monotherapy, with oral administration once daily for 14 days, followed by a 7 day washout. The company announced that these results, along with those from other phase II studies, would be used to establish proof-of-principle for talabostat.

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 11, 2004

Viragen has reported positive results of a seven-year follow-up to a phase II/II study of Multiferon (human alpha-interferon), for the treatment of malignant melanoma following surgical resection. Results showed a statistically significant increase in overall survival among high risk subjects, with 51.3% survival among those receiving adjuvant therapy of Multiferon plus dacarbazine chemotherapy, compared with 30.3% undergoing surgery alone (p=0.0077). This open-label extension follows a controlled, randomized phase II/III trial in Germany, which investigated the efficacy of Multiferon following dacarbazine treatment vs. resection alone following surgery. This earlier trial formed the basis for the approval of Multiferon in Sweden for malignant melanoma following surgical resection, and Viragen announced that it would submit regulatory filings for the first line treatment of malignant melanoma, based upon the results of this seven year extension.

September 27, 2004

Maxim Pharmaceuticals has issued negative results of a phase III trial of their investigational immunosupportive drug Ceplene, for the treatment of malignant melanoma. The trial failed to meet its primary endpoint, with no significant increase in patient survival among subjects receiving Ceplene plus Interleukin-2 (IL-2), versus subjects receiving IL-2 alone. This trial was conducted as an extension of a previous trial, which found a significant improvement in patient survival at one, two and three years among a subgroup of its trial population, advanced malignant melanoma patients with liver metastases; results among the entire trial population of this earlier trial were non-significant. This multicenter, randomized, approved-therapy controlled study enrolled 235 subjects across 35 sites in North America and Europe, all of whom had advanced malignant melanoma with liver metastases. Maxim announced that they intended to continue the development of Ceplene for other cancer indications, and announced that data analysis for this trial was ongoing.

OSI, Genentech, and Roche have announced the results of a phase III trial of Tarceva, their HER1/EGFR tyrosine kinase inhibitor, for the treatment of pancreatic cancer. Data demonstrated that a combination of Tarceva plus gemcitabine chemotherapy improved outcomes versus gemcitabine plus placebo, with a significant improvement in overall survival of 23.5%. In addition, Tarceva-plus-gemcitabine produced significant improvements in risk of death, median survival time, percentage of subjects reaching one year survival, and progression free survival time. No significant difference was observed in tumor response. This randomized, double-blind, placebo-controlled study enrolled a total of 569 subjects with advanced metastatic pancreatic cancer at investigative sites worldwide; all subjects received a standard regimen of gemcitabine chemotherapy, plus one of two doses of Tarceva daily or placebo. The companies announced that following final review and publication of trial data, they would be presented to the FDA to determine the next steps for Tarceva’s development in this indication. An NDA for Tarceva is currently under review by the FDA, for second-line monotherapy treatment of advanced non-small cell lung cancer.

Pharmacyclics announced interim results of their phase I trial of Xcytrin for the treatment of non-Hodgkin’s lymphoma. Data from the ongoing study indicate that the addition of Xcytrin to standard therapy (Rituxan-plus-Zevalin) produced no additional safety concerns or adverse effects in any subjects to date. Furthermore, all three subjects treated to date demonstrated complete remission within one month of treatment initiation; one patient experienced remission for nine months, before a localized relapse, and two have experienced continuing remission for two months. Subjects received a single injection of Rituxan and four daily injections of Xcytrin, followed by a second injection of Rituxan coupled with an injection of Zevalin and four more daily treatments with Xcytrin one week later. This open label study plans to enroll a total of 20 treatment-refractory subjects; all three subjects treated to date had failed three previous treatment courses, including Rituxan monotherapy. Pharmacyclics announced their support of ongoing phase I and II trials in a range on cancers.

September 20, 2004

Cytos Biotechnology issued positive results from their first phase I study of their immunostimulatory drug QbG10, which consist of an antigenic virus-like particle (Qb) coupled to an immunogenic DNA sequence (G10). Results demonstrated that treatment with the drug was safe and well tolerated, with no serious adverse events; the most common minor event was a mild, transient injection site reaction. The study also found the drug to be significantly immunogenic, with high levels of Qb-specific antibodies observed in all evaluable subjects receiving QbG10. Further, Qb-specific T-cells were detected, in a concentration comparable to those observed in a normal antiviral response, in all subjects receiving QbG10 plus Alum, and 73% of subjects receiving QbG10 without Alum. No anti-Qb immune response was observed in the placebo group. This single-center study randomized a total of 35 healthy subjects, who received one of 5 regimens of QbG10 or placebo. Cytos announced plans to initiate a phase II study of QbG10 in the immunological treatment of allergy in late 2004, and a phase I/II study in the immunological treatment of malignant melanoma in the second half of 2005.

September 22, 2003

Dendreon reported mixed preliminary results from a phase III trial investigating Provenge, a recombinant antigen therapy for the treatment of prostate cancer. Data showed that subjects in the Provenge group did not reach statistical significance in the primary endpoint of the study, a delay in time to disease progression, as measured by the Kaplan-Meier method. Results of survival data showed a median survival of 26.3 months in the subjects taking Provenge compared with 19.3 months with placebo. The randomized, double blind, placebo controlled study enrolled 167 men and was designed to measure time to disease progression and time to development of disease-related pain in subjects with androgen independent prostate cancer. Final survival data from D9901 is anticipated to be available in late 2004 to early 2005.

Genta and Aventis reported positive results from a phase III trial investigating Genasense (oblimersen sodium) plus chemotherapy for the treatment of malignant melanoma. Results showed that the addition of Genasense to dacarbazine resulted in a median survival of 9.1 months, compared with 7.9 months for subjects treated with dacarbazine alone. Subjects treated with Genasense plus dacarbazine achieved an antitumor response rate of 11.7% (using RECIST criteria), compared with 6.8% with dacarbazine alone. The randomized study enrolled 771 chemotherapy naïve subjects at 140 sites from 12 countries. The primary endpoint was to compare the overall survival between the two treatment arms. Secondary endpoints included comparative analyses of progression-free survival and tumor response.

March 31, 2003

Genzyme Molecular Oncology reported some positive results from 2 phase I/II trials investigating their patient specific dendritic cell vaccine for the treatment of kidney cancer and melanoma. Results from the metastatic kidney cancer study showed that a majority of the subjects achieved immunological responses from the treatment. Four of the thirteen subjects vaccinated achieved stable disease. One subject remained stable for more than seven months following treatment. No serious adverse events were reported and non-serious adverse events were mild. Results from the metastatic melanoma study showed that only a minority of the subjects achieved an immunological response and no subjects achieved a clinical response. No serious adverse events were report and mild events included injection site reactions, muscle twitching, bruising, and skin redness.

January 13, 2003

BioVex reported positive preliminay results from a phase I trial investigating OncoVex (GM-Csf), an oncoloytic virus for the treatment of breast cancer and melanoma. Data showed that OncoVex caused tumor cells to secrete GM-CSF, which induced tumor necrosis and inflammation. Study results also showed the drug was well tolerated and presented anti-tumor activity at low doses. The primary goal of the study was to determine overall safety and to reveal indications of biological activity. The trial design included a single dose escalation phase to be given to groups of four subjects with metastatic cancer at each dose.

Genzyme Molecular Oncology reported positive results from a phase I/II trial investigating their melanoma cancer vaccine carried in an adenovirus vector. Data showed the vaccine produced clinical or immunologic responses in 71% (15/21) of the subjects treated. The study also showed that 38% of subjects (8/21) showed an immunological response at the sites of vaccination, 23.8% (5/21) experienced skin depigmentation and 14.2% exhibited asymptomatic changes in their retinas. Three subjects exhibited a clinical response, with one of them exhibiting an ongoing pathologic complete response after 18 months. The second subject demonstrated a partial response and the third showed stable disease after a ten-month duration. Treatment related adverse events were mild or moderate most of which were flu-like and flu-related symptoms. The study enrolled 27 subjects with locally advanced or metastatic melanoma, the majority of whom had received prior treatments.

November 25, 2002

GenVec reported positive results from a phase Ib trial investigating TNFerade for the treatment of cancer. The study was designed to test the safety and efficacy of TNFerade in 63 subjects with a wide variety of cancers. The data showed 73% of subjects showed objective tumor shrinkage, their tumors shrank between 25% and 100%, with TNFerade therapy. The objective tumor responses were shown to be: Complete Response (CR) 16.6% of subjects, Partial Response (PR) 30% of subjects and Minor Response (MR) 26% of subjects. Among the subjects with pancreatic cancer, 75% showed tumor shrinkage and one subject showed no disease progression after 18 months. TNFerade was well tolerated and side effects were all classified as mild.

Maxim Pharmaceuticals reported positive results from a phase II trial investigating Ceplene (histamine dihydrochloride) with interleukin-2 (Il-2) for the treatment of advanced metastatic melanoma. The treatment significantly increased the expression of CD3 zeta in T cells and Natural Killer (NK) cells. Treatment with Ceplene and IL-2 also resulted in a decrease in the production of IL-6, a pro-inflammatory cytokine associated with the down-regulation of T cells and NK cells. The study, which enrolled a total of 50 subjects, was designed to investigate the effect of Ceplene and IL-2 on the expression of specific cellular markers that may be associated with the function of key immune cells.

March 25, 2002

Phase II/III trial results indicate that adjuvant treatment with Viragen's natural interferon alpha increases the probability of five-year relapse-free survival (RFS) in subjects with melanoma. The trial, which was conducted at 20 sites in Germany, included subjects with malignant melanoma (stage IIb/IIIa/IIIb) who had undergone complete tumor surgery. Subjects received either two courses of dacarbazine followed by a six-month treatment with low-dose natural interferon alpha or no adjuvant treatment. Estimated five-year RFS rates were 42% and 17% for the treatment and control groups, respectively. Additionally, natural interferon treatment produced a median RFS of 552 days, compared to 174 days for the control group.

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