On November 4, 2014 Exelixis reported positive top-line results from a randomized phase 2 trial of cabozantinib and erlotinib alone or in combination as second- or third-line therapy in patients with stage IV EGFR wild-type non-small cell lung cancer (NSCLC) (Press release Exelixis, NOV 4, 2014, View Source [SID:1234500919]). This trial (Study E1512) is sponsored by the U.S. National Cancer Institute (NCI) through a Cooperative Research and Development Agreement between the Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, NCI and Exelixis. Study E1512 was designed and is being conducted by the ECOG-ACRIN Cancer Research Group as part of Exelixis’ collaboration with the NCI. Joel Neal, M.D., Ph.D., from ECOG-ACRIN member institution Stanford University/Stanford Cancer Institute, chairs the study.

In the E1512 trial, 125 patients were randomized to one of the three arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim ECOG-ACRIN Data Safety Monitoring Committee analysis for futility, it was found that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and also with the combination of cabozantinib plus erlotinib, as compared to erlotinib alone, and the results were highly statistically significant. Safety data were consistent with those observed in other trials of cabozantinib. At time of analysis, the median follow-up was 5.9 months and overall survival data were immature.

The results of the trial are the subject of ongoing analyses and will be submitted by the investigators for presentation at a future medical conference.

Exelixis President and CEO, Michael M. Morrissey, Ph.D., commented on the results: “This is one of the first substantial data sets from our collaboration with NCI-CTEP, which has enabled us to broaden the cabozantinib development program while focusing our internal resources on our pivotal trials. We are excited by these positive results and are looking forward to working with the trial investigators to support future development of cabozantinib in NSCLC and beyond, while we await top-line results from our pivotal phase 3 trial METEOR in metastatic renal cell carcinoma, now anticipated in the second quarter of 2015.”

On November 4, 2014 Amgen reported the top-line secondary endpoint results of overall survival from the Phase 3 TRINOVA-1 trial in women with recurrent platinum-resistant ovarian cancer (Press release, Amgen, NOV 4, 2014, View Source [SID:1234500917]). The study, which evaluated trebananib plus paclitaxel versus placebo plus paclitaxel, did not demonstrate a statistically significant improvement in overall survival. Median overall survival was 19.3 months in the trebananib arm versus 18.3 months in the control arm. The data will be submitted to a future medical conference and for publication.

In the previously reported primary endpoint analysis, the data demonstrated a statistically significant difference in progression-free survival for trebananib. In that analysis, patients treated with trebananib showed a 34 percent reduction in the risk of disease progression or death (HR = 0.66, 95 percent CI, 0.57, 0.77, p<0.001). The median progression-free survival was 7.2 months in the trebananib arm versus 5.4 months in the control arm. "While the overall survival results of the TRINOVA-1 study are disappointing, this study is the first of three Phase 3 trials designed to evaluate the safety and efficacy of trebananib in patients with ovarian cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We continue to explore the potential of trebananib's novel anti-tumor mechanism of action in other cancer settings." In the trebananib arm, the most frequently reported adverse events were localized edema, nausea and alopecia. The rate of discontinuation of investigational product due to adverse events was 20 percent in the trebananib arm versus seven percent in the control arm. No new safety signals were detected. Data from another trial in the recurrent platinum-resistant population (TRINOVA-2) is expected in Q4 2014. Data from a trial evaluating trebananib in combination with first-line chemotherapy treatment for patients with ovarian cancer (TRINOVA-3) is expected in 2015. TRINOVA-1 Trial Design (NCT01204749) TRINOVA-1 (A Study of AMG 386 or Placebo, in Combination With Weekly Paclitaxel Chemotherapy, as Treatment for Ovarian Cancer, Primary Peritoneal Cancer and Fallopian Tube Cancer) is a Phase 3 global, multicenter, randomized, double-blind, placebo-controlled study evaluating trebananib in over 900 women with recurrent partially platinum-sensitive or -resistant (platinum-free interval of 12 months or less) epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients were randomized 1:1 to receive either 15 mg/kg of intravenous trebananib weekly plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off) or weekly intravenous placebo plus 80 mg/m2 of intravenous paclitaxel weekly (three weeks on, one week off). Other ongoing Phase 3 studies of trebananib include TRINOVA-2 and TRINOVA-3. TRINOVA-2 is evaluating whether trebananib plus pegylated liposomal doxorubicin (PLD) is superior to placebo plus PLD as measured by progression-free survival in recurrent epithelial ovarian, primary peritoneal or fallopian tube cancer. TRINOVA-3 is evaluating trebananib or placebo in combination with paclitaxel and carboplatin in the first-line treatment of epithelial ovarian, primary peritoneal or fallopian tube cancer.

On November 2, 2014 Nymox Pharmaceutical reported that the Company’s two Phase 3 U.S. studies of NX-1207 for the treatment of BPH, NX02-0017 and NX02-0018, failed to meet their primary efficacy endpoints. Full results will be reported at a later date (Press release Nymox, NOV 2, 2014, View Source [SID:1234500899]). The Company will hold a teleconference for shareholders on Monday, November 3, 2014 at 4:30 pm Eastern Time. The phone number to call for the teleconference is 1-866-436-9172 for U.S and 1-630-691-2760 for Canada and International. The confirmation number: 38420531.

Nymox CEO, Paul Averback, said, “The two studies failed to meet the pre-specified efficacy endpoints. Drug safety was acceptable. Drug efficacy reached levels similar to earlier studies but was not statistically significant in comparison to the placebo control due to a higher placebo response than in earlier NX-1207 studies and in other placebo-controlled BPH studies. The compound remains promising for low grade localized prostate cancer where the Phase 2 results showed evidence that NX-1207 treatment had a positive effect on biopsy results and clinical and biochemical progression.”