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.”

On October 28, 2014 Bristol-Myers Squibb Company and F-star Alpha reported that the companies, together with the F-star Alpha Ltd. shareholders, have entered into an agreement that provides Bristol-Myers Squibb the exclusive option to acquire F-star Alpha Ltd, and gain worldwide rights to its lead asset FS102 (Press release Bristol-Myers Squibb, OCT 28, 2014, View Source [SID:1234500884]). FS102 is a novel Phase 1 ready Human Epidermal growth factor Receptor 2 (HER2)-targeted therapy in development for the treatment of breast and gastric cancer among a well-defined population of HER2-positive patients who do not respond or become resistant to current therapies.

“This agreement is consistent with our R&D strategy to develop promising treatments that address areas of high unmet medical need, and provides the opportunity to complement our oncology portfolio with a novel targeted therapy,” said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer, Bristol-Myers Squibb. “We look forward to working with F-star and leveraging our broad clinical expertise in oncology to uncover the full potential of FS102.”

“We are thrilled that a company with the oncology experience and expertise of Bristol-Myers Squibb will be advancing our first clinical asset with the potential to provide a significant improvement over the current standard of care for a defined group of patients with HER2-positive cancer,” said John Haurum, M.D., D.Phil., chief executive officer at F-star Biotechnology Ltd. “In addition to the important improvement of cancer therapy FS102 may provide to patients, this program also provides validation of the Modular Antibody Technology platform as a powerful engine to discover and rapidly develop novel targeted biologics.”

HER2 is a highly validated target in breast and gastric cancers, and plays a significant role in the growth of tumors and subsequent poor clinical outcome for patients with breast cancer and other solid tumors. Therapies that target HER2 have shown success in improving patient outcomes; however, a high proportion of HER2-positive patients do not respond to currently available treatments, and those who do may eventually develop resistance.

FS102 is a HER2 targeted Fcab that has the potential to eliminate cancer cells through a novel mechanism of action in a biomarker-defined patient population. FS102 works differently than current HER2-targeted therapies, with the potential to overcome resistance that has developed against other HER2-targeted drugs. It binds to a unique site on HER2 and then induces programmed cell death in HER2-positive tumour cells. In preclinical studies, FS102 has demonstrated encouraging efficacy against certain HER2-positive cancers and major regression in tumors, including those that are refractory to treatment with trastuzumab plus pertuzumab.

Under the terms of the agreement, Bristol-Myers Squibb will make payments aggregating to $50 million that consist of an option fee for the right to acquire F-star Alpha Ltd., payment for certain rights and licenses from F-star Alpha Ltd. and a clinical milestone payment upon initiation of the Phase 1 trial. Bristol-Myers Squibb will be responsible for conducting and funding development of FS102 during the option period. Bristol-Myers Squibb can exercise the option to acquire F-star Alpha Ltd. in its sole discretion upon its decision to commence a Phase 2b trial. Total aggregate consideration may reach $475 million, which includes the payments aggregating to $50 million, the option exercise fee, and milestone payments upon the commencement of a Phase 3 clinical trial and regulatory approvals in the U.S. and Europe.