Clinical Trials Resource Center

Metastatic Cancer

February 9, 2015

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.

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 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.

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.

November 26, 2007

Keryx released positive interim results from a phase II trial of perifosine for the treatment of recurrent malignant glioma. This trial enrolled twenty-five subjects who had failed prior radiation therapy and had evidence of tumor progression. The subjects were treated with a loading dose of 600 mg (150mg x 4) followed by 100 mg daily dose of perifosine. Response was measured by the MacDonald Criteria (partial response greater than or equal to 50% decrease in bidirectional tumor area and stable disease = between 25% worse to 50% better). Out of twenty evaluable subjects, partial response was observed in two, stable disease was observed in four and overall response (partial + stable) was reported in six subjects. The median progression free survival and overall survival was nine weeks and forty-nine weeks, respectively. Treatment was generally well tolerated. Subjects with anaplastic gliomas showed the greatest response, hence the trial planned to continue enrolling only this population.

August 13, 2007

Oxford BioMedica reported positive results from a phase II trial of TroVax for the treatment of metastatic colorectal cancer. This trial was designed to evaluate the safety and immunogenicity of TroVax when administered with chemotherapy. The trial enrolled 17 subjects who received the vaccine before, during and after the standard chemotherapy regimen FOLFOX. A course of treatment consisted of six vaccinations. Throughout the study, subjects were monitored for an immune response to 5T4. Eleven of the 17 subjects who had completed a course of treatment mounted a strong immune response to 5T4. Of these 11 subjects, six showed significant tumor shrinkage and one no longer had any detectable tumors. The overall median survival was 68 weeks in all 17 vaccinated subjects and 118 weeks in the 11 subjects who received all six vaccinations. Additional phase II and III trials are ongoing at this time.

January 29, 2007

BTG issued positive results from a phase I/II trial of plevitrexed for the treatment of metastatic gastric cancer. The phase I portion of this trial enrolled 30 subjects who received plevitrexed at doses of 65 mg/m2, 130 mg/m2 and 165 mg/m2 on days 1 and 8 of a 3-week cycle in combination with nutritional levels of folic acid and vitamin B12. This part of the trial was designed to evaluate the safety, tolerability and maximum tolerated dose (MTD) for the phase II portion, which enrolled an additional 25 subjects and was designed to evaluate efficacy. Treatment was well tolerated with no reported serious adverse events. The MTD was determined to be 130 mg/m2. Of the 28 subjects evaluable for efficacy at this dose level, five (17.9%) had partial response and 15 (53.6%) had stable disease, for an overall disease control rate of 71.4%. One subject treated with plevitrexed at a lower dose of 65 mg/m2 had a complete response and five subjects who received a higher dose of 165 mg/m2 had stable disease. The median progression free survival rate was 120 days and the median overall survival was 239 days. Based on these results, BTG plans to seek a partner to complete the clinical and commercial development of plevitrexed in the treatment of gastric and other types of cancer.

Taiho reported positive interim results from a phase III trial of S-1 for the treatment of gastric cancer. This trial, dubbed ACTS-GC, enrolled 1,059 subjects with stage II or III gastric cancer, in Japan. Subjects were randomized to receive oral S-1 for 12 months at 80-120 mg/day according to the body surface, (administration was 4 weeks on with 2 weeks off in each course, starting within 45 days of surgery until 1 year after surgery), versus curative surgery alone. The primary endpoint was overall survival. Secondary endpoints included relapse free survival and safety. Treatment was generally well tolerated, with the most common reported adverse events including nausea, vomiting and diarrhea. Overall survival at 3-years was 80.5% for subjects receiving S-1 and 70.1% for subjects undergoing surgery alone, with a hazard ratio (HR) of 0.68 (95%CI, 0.52-0.87, p=0.0024). The 3 year relapse free survival was 72.2% in the S-1 arm and 60.1% for surgery alone (p=0.0001) and the reduction of the relative risk of relapse with S-1 was 38% (p < 0.0001). Finally, the relative risk of death for the subjects in the S-1 arm was reduced by 32% as compared to curative surgery alone (p = 0.0024). This drug is currently undergoing phase III trials in the US.

January 15, 2007

Kosan issued positive preliminary results from a phase II trial of tanespimycin plus Herceptin for the treatment of Herceptin-refractory HER2-positive metastatic breast cancer. This trial was designed to determine the objective response rate according to RECIST criteria in subjects with HER2-positive metastatic breast cancer with tumor progression during treatment with one Herceptin-containing regimen immediately prior to entering the trial. The trial enrolled 12 subjects who received tanespimycin (450 mg/m2) via a two-hour weekly intravenous infusion administered along with the standard dose of Herceptin. Treatment was well tolerated, with adverse events mild in nature. Of the eight subjects evaluable for efficacy, five (63%) showed signs of clinical benefit and three who had received 4-6+ cycles of treatment had stable disease. Based on the results Kosan plans to advance the development of tanespimycin into phase III trials.

Vertex and Merck announced positive results from a phase I trial of VX-680 (MK-0457) for the treatment of resistant leukemias and myeloproliferative diseases. This trial enrolled 44 subjects with chronic myelogenous leukemia (CML), Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL), or myeloproliferative diseases (MPD). Subjects were treated with VX-680 given as a five-day intravenous infusion every two-to-three weeks. No treatment related toxicities were reported and thus the maximum tolerated dose was not yet determined. Out of the 15 subjects with CML, nine had a T315I BCR-ABL mutation. Eight of these nine T315I subjects had either a hematologic and/or cytogenetic response to VX-680 following multiple cycles of treatment. The six subjects without the T315I BCR-ABL mutation did not exhibit any clinical responses. In addition, two subjects in the study with Ph+ ALL carrying the T315I mutation had either hematologic and/or cytogenetic responses, including one who had a clinical response with a full molecular remission. Six of the nine subjects with MPD having the V617F activating mutation in JAK-2 also had clinical responses. Based on these results, a phase II trial is planned for January of 2007.

January 9, 2006

Allos Therapeutics announced positive results of a phase III study, dubbed REACH, of Efaproxyn (efaproxiral) for the treatment of brain metastases. Trial data indicated that the drug significantly decreased risk of death by 25% in combination with whole-brain radiation therapy (WBRT) and supplemental oxygen (SO), compared to WBRT plus SO alone (p=0.01). Subpopulation analysis of patients with brain metastases due to non-small cell lung cancer or breast cancer indicated a significant improvement in response rate (13%; p=0.01), and a trend towards improvement in median survival time in (38% improvement; p=0.07). Treatment with the drug was generally well tolerated, with most adverse events being mild to moderate (grade 1 or 2) in severity. This randomized, open-label study enrolled 538 patients, who received a regimen of WBRT plus SO alone (n=267), or in combination with Efaproxyn (n=271).

January 2, 2006

Pharmacyclics announced top-line results of a phase III trial of Xcytrin (motexafin), for the treatment of brain metastases in subjects with non-small cell lung cancer (NSCLC). Trial data failed to demonstrate significant improvement in time to neurological progression (15.4 months vs. 10.0 months for placebo; p=0.122). Further, no improvements were noted in overall survival or several other secondary endpoints, though reduction in steroid use trended positively. North American subjects did yield significant improvements (24.2 months vs. 8.8 months; p=0.004). This randomized, controlled study enrolled 554 patients across 94 site in North America, Europe and Australia.

April 25, 2005

Adventrx Pharmaceuticals reported results of a phase II trial of CoFactor (CH2FH4), in combination with 5- fluorouracil (5-FU), for the treatment of colorectal cancer. Toxicity and pharmacodynamic data indicated a positive toxicity profile based on a laboratory measures. Specifically, administration of CoFactor produced an increase producing increases in RBC folate pool expansion (form a mean baseline score of 533 ng/ml to a score of 1295 ng/ml following weekly dosing), urinary folate excretion (an indication of formaldehyde toxicity) showed a small decrease (from a baseline historical baseline of 5 ug/ml to a post-treatment mean of 3.7 ug/ml). These data support the use of CoFactor in combination with 5-FU to improve efficacy and reduce toxicity. This open-label study enrolled subjects with metastatic colorectal cancer, and was designed to investigate several laboratory measures of the toxicity associated with CoFactor administration and metabolism, in the hopes that the drug in combination with 5-FU will provide better efficacy and reduced toxicity, compared to standard therapy of 5-FU and leucovorin. The company announced that these data would serve to support upcoming phase IIb and III trials in the UK and the US.

Agennix reported positive results of a phase II trial of talactoferrin alpha in combination with chemotherapy, for the first line treatment of non-small cell lung cancer (NSCLC). Results from the study found that the addition of talactoferrin significantly improved overall response rate vs. placebo. Specifically, overall response rate in the prospectively defined evaluable patient group was 47%, vs. 29% for placebo (p= 0.05). The addition of talactoferrin was also well tolerated, with no evidence of increased toxicity. This double-blind, placebo- controlled study enrolled 110 treatment-naïve NSCLC patients, who were randomized 1:1 to receive talactoferrin or placebo, in combination with a standard chemotherapeutic regimen of carboplatin/paclitaxel.

Human Genome Sciences reported positive results of an ongoing phase I trial of their investigational TRAIL-1 monoclonal antibody HGS-ETR1, for the treatment of solid tumors. Trial data met their safety endpoints, with the highest dose acceptably tolerated and a generally mild (Grade 1 or 2) adverse event profile. Pharmacokinetics were proportional to dose, and mean elimination half-life was 17 days. Efficacy was also noted, with 10 instances of stable disease, including one subject who had received 16 treatments with the drug. This open-label, multi-center, dose- escalation trial had enrolled 44 heavily pretreated subjects to date (median prior chemotherapeutic regimens: 6), who received one of 7 IV doses of the drug (0.01, 0.03, 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg), once every 14 or 28 days.

Medarex and Bristol-Myers Squibb reported positive results of a phase II study of their investigational two-drug therapy for metastatic melanoma, which includes the anti-CTLA-4 antibody MDX-010 and the gp100 melanoma vaccine MDX-1379. Both trial dosing regimens yielded evidence of efficacy, with 2 complete responses (ongoing through 30 and 31 months) and 2 partial responses (4 months; ongoing through 34 months) in cohort 1, and 3 partial responses (6 months; ongoing through 25 and 26 months) in cohort 2. Serious Grade III/IV adverse events occurred more often in cohort 1 (n=9) than cohort 2 (n=5). This two- armed open-label study enrolled 56 subjects with metastatic melanoma, who received MDX-1379 plus 3.0 mg/kg MDX-010 every 3 weeks (cohort 1; n=29), or MDX-1379 plus an initial 3.0 mg/kg dose of MDX-010, followed by 1.0 mg/kg every 3 weeks (cohort 2; n=27).

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.

March 7, 2005

American Pharmaceutical Partners presented positive data from a phase III study of their recently approved drug Abraxane (albumin-bound paclitaxel particles), for the treatment of metastatic breast cancer at the 22nd Annual Miami Breast Cancer Conference. Study results yielded significant evidence of efficacy, with second-line patients receiving Abraxane experiencing significantly improved median survival times, vs. those receiving unmodified paclitaxel (56.4 weeks vs. 46.7 weeks; p=0.016); this response corresponded to a 29% reduction in risk of death. A non-significant improvement vs. paclitaxel was observed in the overall patient population, including both second-line-or-later subjects (65.0 weeks vs. 55.7 weeks). The drug maintained its advantageous tolerability profile, with no unexpected serious adverse events and no hypersensitivity reactions. This approved-therapy controlled study enrolled a total of 460 patients, who received either 260 mg/m2 Abraxane via 30 minute infusion with no premedication or 175 mg/m2 paclitaxel via 3 hour infusion with hypersensitivity-suppressing premedication including steroids and antihistamines.

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.

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.

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.

July 12, 2004

Celgene has published positive results of a phase II trial of Thalomid (thalidomide), in combination with docetaxel (taxotere), for the treatment of metastatic androgen-independent prostate cancer (AIPC). Thalomid is currently approved for the treatment of leprosy. Data from the trial indicated that the addition of Thalomid to standard docetaxel therapy produced both significant and non significant improvements in several disease measures. The trial enrolled 75 prostate cancer patients, all of whom received docetaxel infusions once weekly for 3 of 4 weeks; 50 subjects were also treated daily with orally administered Thalomid. Addition of Thalomid produced significant increases in the number of patients who experienced a greater-than-50%-reduction in prostate-specific antigen levels, and in median overall survival time. Non-significant improvements were seen in 18-month survival rates (68.2% vs. 42.9%, p=0.11) and median progression free survival time (5.9 months vs. 3.7 months, p=0.32). Celgene announced plans to continue clinical development of Thalomid for this indication.

Cell Genesys has reported positive initial results of their phase II trial of GVAX, their anti-cancer vaccine therapy, for the treatment of inoperable, treatment-refractory metastatic pancreatic cancer. Trial data have indicated that the vaccine may be effective in improving survival time and promoting stable disease state, even in this difficult to treat population. 50 subjects, the majority of whom had failed at least two regimens of chemotherapy, were treated with up to 6 doses of the GVAX vaccine; 20 of these subjects also received low doses of the chemotherapeutic cyclophosphamide, at sub-therapeutic levels associated with generating an immune response. The group receiving the combination of drugs demonstrated trends towards improvement in disease stability, median time to progression and median survival time, compared with GVAX alone. A second phase II trial of GVAX, in patients with operable pancreatic cancer, is ongoing, with results expected during 2005.

June 14, 2004

Aesgen reported positive results of their phase III study of Saforis (L-glutamine) for the treatment of oral mucositis in cancer patients receiving chemotherapy. Results showed that Saforis significantly reduced the severity and duration of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy regimens versus placebo. Utilizing two sequential treatment cycles, subjects received either Saforis-then-placebo or placebo-then-Saforis. In the first cycle, Saforis subjects showed a 22% reduced incidence of moderate-to-severe oral mucositis, and when this group was switched to placebo during the second treatment cycle, incidence of oral mucositis was 36% below baseline. The multi-center study enrolled 326 evaluable subjects. Based on these results, Aesgen announced plans to file a NDA under their Fast Track designation in the near future.

GlaxoSmithKline reported positive interim results of their phase II study investigating lapatinib, an inhibitor of two receptor tyrosine kinases (ErbB1/EGFR and ErbB2), for the treatment of refractory metastatic breast cancer. Preliminary results from the first 41 subjects indicated that a once daily oral dose of lapatinib might effect an improved or stable disease state in women with breast cancer refractory to standard treatment regimens including Herceptin (trastuzumab). The study found that 46% (n=19) of the evaluated patients had stable or improved disease state at 8 weeks, and 24% (n=10) at 16 weeks. The ongoing multi-center, open label study plans to enroll a total of 80 women with breast cancer over-expressing ErbB2, all of whose disease had been refractory to treatment regimens including Herceptin, an FDA approved monoclonal ErbB2 antibody. If final results confirm the interim analysis, GlaxoSmithKline plans to use this trial to support ongoing trials of lapatinib in multiple ErbB2-expressing solid tumors.

ImClone Systems and Merck KGaA reported negative results from a phase III trial investigating IMC-BEC2, an anti-idiotypic monoclonal antibody cancer vaccine for the treatment of small cell lung cancer (SCLC). Results showed the vaccine trial did not meet its primary endpoint of survival. The international, randomized study was designed to assess the survival benefit of vaccination with IMC-BEC2 and the immune stimulant BCG over a two-year period. Subjects received IMC-BEC2/BCG vaccination or were only monitored in the observation arm. The study was conducted in collaboration with the European Organization for Research and Treatment of Cancer. Both companies intend to meet to discuss the future of the IMC-BEC2 development program.

OncoGenex and Isis announced positive results of a phase I study of OGX-011, an antisense clusterin inhibitor, for the treatment of prostate cancer. Results indicated that the drug achieved high concentration in target tissues and successfully dose-dependently down-regulated the expression of clusterin, a cell survival mediator. The study was designed to assess the bioavailability, tissue specificity and optimum dosing regimen of weekly IV infusions of OGX-011 in subjects with localized prostate cancer over 4 weeks. Immunostaining revealed availability of OGX-011 in the target tissue, and a 91% reduction in clusterin at the highest dose level (640 mg); this dose was determined to be optimum for future studies. The study enrolled a total of 25 subjects eligible for prostatectomy, all of whom underwent the surgery following the trial. OncoGenex and Isis planned to use the dosing information obtained in this trial to support the initiation of a phase II study later this year.

Therion Biologics reported results from two phase I trials investigating PANVAC-VF, a therapeutic cancer vaccine for the treatment of pancreatic cancer. The subcutaneously administered vaccine is designed to stimulate the immune system to target and destroy cancer cells expressing the carcinoembryonic antigen (CEA) and mucin -1 (MUC-1). Results showed a median overall survival of 7.9 months and at least 5.3 months, respectively, compared to an historical median overall survival of approximately 3.0 months. In addition, 33% of subjects in the study remain alive at 13 months. No serious adverse events related to the vaccines were reported. Common side effects included fever, chills and fatigue. The open label studies enrolled a total of 22 subjects with advanced (Stage III or IV) pancreatic cancer who had received prior chemotherapy. Due to these positive results, Therion will conduct a pivotal phase III trial with PANVAC-VF in the summer of 2004.

January 26, 2004

Pharmacyclics reported positive results from a phase III trial investigating Xcytrin (motexafin gadolinium) in combination with whole brain radiation therapy (WBRT) for the treatment of brain metastases in lung cancer patients. Results showed that Xcytrin significantly prolong the time to neurologic progression, determined by investigators and a review committee The randomized, controlled trial enrolled 401 subjects with metastatic cancer to the brain and was designed to compare the effects of WBRT alone to WBRT plus Xcytrin. Results were reported in the January issue of the Journal of Clinical Oncology (JCO). Based on these results, Pharmacyclics initiated a pivotal phase III trial, called SMART (Study of Neurologic Progression with Motexafin Gadolinium And Radiation Therapy) in the U.S., Canada, Europe and Australia.

December 8, 2003

Allos Therapeutics reported positive results from a phase III trial investigating RSR13 (efaproxiral), a radiation sensitizer for the treatment of cancer. The results demonstrate a significant survival benefit for women with breast cancer and brain metastases who received RSR13 plus whole brain radiation therapy (WBRT) versus WBRT alone. Data showed that subjects treated with RSR13 plus WBRT achieved a higher response rate in the brain than the control group (71.7% vs. 49.1). Subjects reported minimal serious adverse events with the most common being hypoxemia. The open-label, comparative, randomized study enrolled 538 subjects. Results were reported at the 26th Annual San Antonio Breast Cancer Symposium.

Genentech and Roche reported positive results from a phase II trial investigating Herceptin (Trastuzumab) in combination with Taxotere (docetaxel) as a first-line treatment for breast cancer. Results showed that the overall response rate for subjects with Herceptin plus docetaxel was significantly increased. Data showed that 61% of subjects who received Herceptin and docetaxel (100 mg/m2 every 3 weeks for at least 6 cycles) responded compared to 36% with docetaxel alone. The multi-center, randomized study enrolled 188 patients who had evidence of HER2-positive disease. Subjects received Herceptin (2mg/kg weekly) plus docetaxel or docetaxel alone. Results were reported at the 26th Annual San Antonio Breast Cancer Symposium.

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.

July 28, 2003

PRIMABioMed Limited reported positive results from a phase Ib trial investigating their Cancer Vac immunotherapy for the treatment of various advanced cancers. Results showed that two subjects who have now continued therapy for 18 months have experienced no progression of their disease. One subject with ovarian cancer showed that their disease marker, which was rising before administration of the immunotherapy, was halted and maintained at a stable level. Tumors in the second subject, with kidney cancer, have also remained stable for over a year. All subjects demonstrated an ability to produce an immune response to the tumor protein. The 12-week study enrolled 12 subjects in Australia. The Cancer Vac therapy involves extracting blood cells, manipulating the immune cells by exposing them to the immunotherapeutic product and then re-injecting these cells to induce a specific immune response.

June 23, 2003

Biomira and Merck KGaA reported negative results from a phase III trial investigating Theratope, a vaccine for women with metastatic breast cancer. Results demonstrated that treatment did not meet statistical significance in the primary endpoints of time to disease progession and overall survival. One subset of women, placed on hormonal treatment following chemotherapy, showed a favourable trend in survival improvement. The randomized, double blind trial enrolled 1,030 subjects and was designed as a survival study. Theratope was well tolerated with the most common side effects being flu-like symptoms and local injection site reactions. Theratope is also being studied in a phase II study of women with metastatic breast cancer being treated with hormone therapy and a Phase II study in men and women for the treatment of colorectal cancer.

June 16, 2003

Dendreon reported additional positive results from a phase III trail investigating Provenge, an investigational therapeutic vaccine for the treatment of metastatic prostate cancer. Results showed that Provenge induced a significant T-cell mediated immune response compared with placebo. Data revealed Provenge treated subjects demonstrated an eight-fold increase in T-cell proliferation compared to placebo treated subjects. The double blind, placebo controlled study enrolled men with androgen independent prostate cancer. Provenge treated men, with a Gleason score of seven or less, developed a median change in T-cell mediated immune response seven-fold greater than those seen men with a Gleason score of eight and higher. No apparent benefit from Provenge therapy was observed among subjects with Gleason scores of eight or higher. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor.

AltaRex reported positive results from a phase III trial investigating OvaRex (oregovamab), a murine monoclonal antibody for the treatment of ovarian cancer. Results showed the time to relapse was 13.3 months with OvaRex compared with 10.3 months with placebo treatment. Subjects with optimal surgical cyto-reduction and no evidence of disease following chemotherapy showed a dramatic clinical benefit as compared to placebo. Subjects with less favorable response to surgery and chemotherapy did not appear to benefit from OvaRex. The randomized, multi-center, placebo-controlled study enrolled 145 subjects following front-line surgery and chemotherapy for stage III/IV ovarian cancer. The side effect profile for OvaRex treatment was similar to placebo.

Genta reported positive preliminary results from a phase II trial investigating Genasense (oblimersen sodium), a BCl-2 protein inhibitor for the treatment of non-Hodgkin’s lymphoma. Results show that across all Genasense treatment groups, 10 of 25 subjects (40%) remained stable without progression during all six treatment cycles. Out of 16 previously treated subjects, one subject (6%) achieved a complete response, and six subjects (38%) achieved stable disease when receiving Genasense alone. During disease progression subjects who were diagnosed and who had not previously received chemotherapy then received a combination of Genasense plus a standard regimen consisting of Rituxan(R), cyclophosphamide, doxorubicin, vincristine, and prednisone. The ongoing study enrolled 37 subjects with mantle cell lymphoma. So far, 25 subjects are evaluable for response; 14 of these patients are still receiving treatment. The study was designed to evaluate the effects of Genasense used without chemotherapy, given every 3-4 weeks.

Spectrum Pharmaceuticals reported positive results from a phase III trial investigating satraplatin, an oral platinum compound for the treatment of prostate cancer. Results demonstrated statistically significant superiority in time to disease progression with satraplatin and a doubling of progression-free survival. The median time to disease progression was 5.2 months for satraplatin versus 2.5 months for the control arm. Data showed a median overall survival time of 15 months for subjects treated in the satraplatin arm versus 12 months for subjects in the control arm. The randomized study 50 subjects with hormone-refractory prostate cancer and evaluated satraplatin plus prednisone versus prednisone alone for use as a first-line chemotherapy treatment. A greater than 50% decline in PSA (prostate-specific antigen) was experienced by 33% (9/27) of subjects in the satraplatin arm versus 9% (2/23) of subjects in the control arm.

SuperGen reported positive results from a phase III trial investigating Orathecin (rubitecan), a topoisomerase I-inhibitor for the treatment of advanced ovarian cancer. Results showed that 7% (13/196) of subjects given Orathecin experienced either a complete or partial tumor response compared with less than 1% (1/211) for subjects receiving an alternative treatment. The median time to disease progression was 57 days for subjects receiving Orathecin, versus 47 days for subjects receiving alternative. The primary study end-point was overall survival, with secondary end-points of tumor response and time to disease progression. Most of subjects in the alternative treatment group received a chemotherapeutic agent such as gemcitabine, 5-FU, mitomycin C, capecitabine, or docetaxel. The randomized, comparative clinical study enrolled 409 subjects with advanced pancreatic cancer.

May 26, 2003

Genentech reported positive results from a phase III trial investigating Avastin (bevacizumab) plus chemotherapy for the treatment of metastatic colorectal cancer. Results showed that the study in previously untreated subjects met its primary endpoint of improving overall survival. Data showed the trial also met the secondary endpoints of progression-free survival, response rate, and duration of response. The multi-center, randomized study enrolled more than 900 subjects to receive either Avastin plus the standard of care chemotherapy (5-FU/Leucovorin/CPT-11, called the Saltz regimen) or the Saltz regimen plus placebo. The addition of Avastin to chemotherapy was well tolerated. The company plans to submit data from this trial to the annual meeting of the American Society of Clinical Oncology, May 31 - June 3.

April 28, 2003

Allos Therapeutics reported mixed preliminary results from a phase III investigating RSR13 (efaproxiral), a radiation sensitizer agent for the treatment of brain metastases. Results showed that the difference in overall survival between subjects who received RSR13 plus whole brain radiation therapy (WBRT) and subjects who received only WBRT was not statistically significant. However, the trial did show a positive survival benefit among subjects with metastatic breast cancer. In addition, subjects receiving RSR13 plus WBRT experienced a 17.6% improvement in median survival length compared to subjects receiving WBRT alone (5.26 vs. 4.47 months). The randomized, open-label, pivotal study enrolled 538 subjects at more than 83 cancer sites worldwide.

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.

December 16, 2002

Titan Pharmaceuticals reported mixed results from a phase III trial investigating CeaVac, a monoclonal antibody for the treatment of metastatic colorectal cancer. CeaVac failed to demonstrate a statistically significant improvement in the primary endpoint of survival in the overall efficacy, but a trend toward 2-3 month survival improvement was shown in subjects receiving at least 5 doses. The randomized, placebo-controlled study enrolled 631 subjects receiving chemotherapy with 5- flourouracil (5-FU) and leucovorin for metastatic colorectal cancer. Subjects in the study received injections of CeaVac once every two weeks for 2 months and then once per month after. Treatment with CeaVac was generally well tolerated, with the most common side effect being local injection site irritation.

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.

November 11, 2002

GlaxoSmithKline reported positive results from a phase II trial of Navelbine (vinorelbine tartrate), a previously approved chemotherapy treatment, with the monoclonal antibody therapy Heceptin (trastuzumab) for the treatment of metastatic breast cancer. An overall response rate of 78% was observed with 4 complete and 25 partial responses reported. The study, designed to determine if the addition of Navelbine would increase the expected response rate to Herceptin, showed an improvement of 4-fold compared to historical data. Additionally, this combination extended the time to disease progression beyond the time shown in Herceptin alone. The multi-center, open-label trial enrolled 40 women with metastatic disease whose tumors over-expressed the HER2Neu oncogene, a growth-promoting protein linked to a poor prognosis in breast cancer.

October 14, 2002

Pharmacyclics reported results from an international, randomized controlled, phase III clinical trial investigating using Xcytrin on non-small cell lung cancer. The researchers concluded that when combined with whole brain radiation therapy (WBRT), Xcytrin significantly slowed the time to neurological progression and decreased deaths due to brain tumor in subjects with brain metastases from lung cancer. There was a significant improvement among the 401 intent-to-treat subject population, with the median time to neurologic progression at 3.8 months with WBRT alone versus 4.3 months with WBRT and Xcytrin. Among lung cancer patients, the median time to neurological progression was 3.7 months with WBRT alone versus 5.5 months with WBRT and Xcytrin. There was a significant reduction in brain tumor deaths among lung cancer subjects with 51% dying after receiving WBRT alone versus 32.2% after receiving WBRT and Xcytrin. Additionally, positive interim results were also reported for Xcytrin in an ongoing phase II clinical trial studying primary brain tumors (glioblastoma multiforme, or GBM).

August 5, 2002

Interim results of a phase II trial of Aphton's G17DT in combination with chemotherapy showed that out of 72 subjects with metastatic stomach cancer who were treated with the investigational drug, 36 had tumor shrinkage of 50% or more, and one subject had a complete tumor response (no detectable residual tumor). The overall tumor response rate was 51.4%. 20 additional subjects had stable disease.

February 19, 2002

Pharmacia reported that they are discontinuing their colorectal cancer clinical trial program for SU5416, a small molecule angiogenesis signaling inhibitor. The decision was based on results from a planned interim analysis of a large phase III study. Data showed that the study would not achieve the defined trial endpoints due to a lack of clinical benefit. The phase III study was designed to evaluate standard chemotherapy treatment with or without SU5416 in patients with advanced stage colorectal cancer. The company will also be working with all other SU5416 study investigators to bring the remaining trials to an appropriate conclusion. The SU5416 program was under development by Sugen, a subsidiary of Pharmacia.

Interim results were reported from 30 subjects in a phase II trial of Aphton's G17DT. The trial is designed to evaluate G17DT in combination with chemotherapy (cisplatin plus 5FU/Leucovorin) in subjects with metastatic gastric cancer. When chemotherapy was administered with G17DT, subjects completed an average of 5.5 cycles of chemotherapy, compared to a normal average of 2.5 cycles prior to discontinuation due to side effects. Results showed an overall response rate of 50% - 14 of the 30 subjects experienced a partial response, and one experienced a complete response.

December 17, 2001

Phase III trial results indicate that first-line therapy with Novartis' Femara (letrozole) improves survival of postmenopausal women with locally advanced or metastatic breast cancer compared to tamoxifen. The randomized, double-blind trial consisted of 907 postmenopausal women, with 453 receiving Femara and 454 receiving tamoxifen. At one and two years, data demonstrated that Femara produced a statistically significant survival advantage compared to tamoxifen. Additionally, in comparison to subjects receiving tamoxifen, those on Femara had a 78% greater chance of responding to treatment. In terms of disease progression, Femara was shown to delay progression for a median of 9.4 months compared to 6.0 months for tamoxifen.

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