On September 30, 2014 OncoMed Pharmaceuticals reported the advancement of the first small molecule Wnt pathway inhibitor under its collaboration with Bayer Pharma AG. The small molecule product candidate is advancing to preclinical development triggering a $2 million milestone payment to OncoMed (Press release OncoMed, SEP 30, 2014, View Source [SID:1234500771]).

John Lewicki, Ph.D., OncoMed’s Chief Scientific Officer, commented, “By combining OncoMed’s anti-cancer stem cell discovery expertise and platform technologies with Bayer’s medicinal chemistry capabilities, we have identified a novel small molecule candidate targeting the Wnt pathway. Early preclinical testing of this molecule’s activity demonstrates robust anti-tumor and anti-cancer stem cell activity that warrants further testing.”

OncoMed and Bayer initiated joint discovery efforts to identify small molecule inhibitors of the Wnt pathway, a key cancer stem cell pathway, as part of the companies’ collaboration initiated in 2010. This is the first small molecule inhibitor of a cancer stem cell pathway from the collaboration to enter preclinical development. Bayer will lead development and commercialization of Wnt small molecule product candidates. As part of this collaboration, OncoMed is leading the advancement of two clinical-stage biologic candidates, vantictumab (anti-FZD7, OMP-18R5) and ipafricept (Fzd8-Fc, OMP-54F28), through multiple Phase 1b studies.

“OncoMed’s biologics targeting the Wnt pathway, vantictumab and ipafricept, have made steady clinical progress, demonstrating potent on-target activity,” said Paul Hastings, Chairman and Chief Executive Officer of OncoMed. “The achievement in the small molecule program is further validation of this important cancer stem cell pathway and the successful alliance between Bayer and OncoMed. We look forward to the continued development of this promising new preclinical candidate.”

On September 29, 2014 Exelixis reported the positive results from coBRIM, the phase 3 pivotal trial (NCT01689519) conducted by Exelixis’ collaborator Genentech, a member of the Roche Group, evaluating cobimetinib, a specific MEK inhibitor discovered by Exelixis, in combination with vemurafenib in previously untreated patients with unresectable locally advanced or metastatic melanoma harboring a BRAF V600 mutation (Press release Exelixis, SEP 29, 2014, View Source [SID:1234500767]).

The trial met its primary endpoint of demonstrating a statistically significant increase in investigator-determined progression-free survival (PFS). The median PFS was 9.9 months for the combination of cobimetinib and vemurafenib versus 6.2 months for vemurafenib alone (hazard ratio [HR]=0.51, 95 percent CI 0.39-0.68; p<0.0001), demonstrating the combination reduced the risk of the disease worsening by half (49 percent). The median PFS by independent review committee (IRC), a secondary endpoint, was 11.3 months for the combination arm compared to 6.0 months for the control arm (HR=0.60, 95 percent CI 0.45-0.79; p=0.0003). Objective response rate (ORR), another secondary endpoint, was 68% for the combination versus 45% for vemurafenib alone (p<0.0001). Overall survival data are not yet mature (HR=0.65, 95 percent CI 0.42-1.00; p=0.046), and at the interim analysis the p-value did not cross the prespecified boundary for significance. The safety profile of the combination was consistent with that observed in a previous study. The coBRIM data will be presented at ESMO (Free ESMO Whitepaper) 2014 today, Monday, September 29, during the Presidential Symposium by Professor Grant McArthur, Peter MacCallum Cancer Centre, Australia (Abstract #LBA5_PR, Monday, September 29, 2014, 4:00-5:20 p.m. CEST) and are also part of the official press program. Additionally, the study was published online today in the New England Journal of Medicine. Roche has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency, and Genentech plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration later this year. "Today’s presentation of data from the coBRIM trial underscore the potential for the combination of cobimetinib, an Exelixis-discovered compound, and vemurafenib to provide significant clinical benefit for patients with previously untreated BRAF V600 mutation-positive advanced melanoma," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "Our partner Genentech sponsored a rigorous and well-run trial, and the results, including a significant increase in PFS and a high objective response rate, are compelling. The regulatory filing process is underway with the submission of the EU filing of the MAA. We look forward to the U.S. filing later this year and then ultimately, if approved, to supporting cobimetinib’s commercialization through our longstanding collaboration that includes a co-promotion component in the United States."

On September 29, 2014 Bristol-Myers Squibb reported that the European Medicines Agency (EMA) has validated for review the Marketing Authorization Application (MAA) for nivolumab in non-small cell lung cancer (NSCLC) – the first completed regulatory submission for a PD-1 immune checkpoint inhibitor in this tumor type (Press release Bristol-Myers Squibb, SEP 29, 2014, View Source [SID:1234500765]).

“Lung cancer is the leading cause of cancer death worldwide, and there remains a significant need for effective treatment options for patients with this disease,” said Michael Giordano, M.D., senior vice president, Head of Oncology Development, Bristol-Myers Squibb. “We are pleased to have two applications for nivolumab now under review in the E.U., and look forward to continued collaboration with health authorities around the world as we work to bring nivolumab to patients.”

The MAA submitted to the EMA in lung cancer is based on data from the Phase 2 study of nivolumab in third-line pre-treated squamous cell NSCLC (Study -063).

In addition to the MAA for lung cancer in the E.U., the company previously announced that it has initiated a rolling submission with the FDA for Opdivo in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end.

On September 27, 2014 Ipsen reported the presentation at the ESMO (Free ESMO Whitepaper) 2014 Congress (26-30 September in Madrid) of the preliminary results of the phase II proof-of-concept clinical trial with tasquinimod in monotherapy, evaluating the compound in four advanced tumor types (Press release Ipsen, SEP 27, 2014, View Source [SID:1234500764]).

The main objective of the study was to determine the clinical activity of tasquinimod in advanced hepatocellular (HCC), ovarian (OC), renal cell (RCC) and gastric (GC) carcinomas in patients who had progressed after standard anti-tumor therapies. Primary endpoint was the PFS rate at a predefined time for each cohort. Secondary objectives included PFS, response rate, OS, safety, pharmacokinetics and biomarkers.

The data did not support further development of tasquinimod in monotherapy in heavily pretreated patients with advanced OC, RCC and GC. Pharmacokinetic and biomarkers analyses are ongoing. Preliminary results from the futility analysis reported sufficient clinical activity to complete the recruitment of the HCC cohort for which results are expected in 2015.
The safety profile was consistent with the known safety profile of tasquinimod in previous studies.

Data from the HCC cohort was presented (Poster p-171)1 at the International Liver Cancer Association 8th Annual Conference (5–7 September 2014, Kyoto, Japan).