Exelixis (EXEL) Announces Presentation of Cobimetinib, Vemurafenib, Atezolizumab Combo Phase 1b Data in BRAF V600

October 7, 2016 7:38 AM EDT

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Exelixis, Inc. (Nasdaq: EXEL) announced that its collaborator Genentech, a member of the Roche Group (OTC: RHHBY), will present preliminary results from a phase 1b clinical trial evaluating the safety and clinical activity of the triple combination of cobimetinib, vemurafenib, and atezolizumab in patients with previously untreated BRAF V600 mutation-positive advanced melanoma. The results will be the subject of a poster discussion presentation (Abstract #1109PD) at the European Society of Medical Oncology (ESMO) 2016 Congress, which is being held October 7-11 in Copenhagen, Denmark. Patrick Hwu, M.D., chair of the Department of Melanoma Medical Oncology at the University of Texas M.D. Anderson Cancer Center, Houston, Texas, will present the results during a session on Monday, October 10, 2016, beginning at 11:00 a.m. CEST.

“Cobimetinib and vemurafenib is FDA-approved to treat specific forms of BRAF V600 mutation-positive unresectable or metastatic melanoma and has been associated with significant improvements in progression-free survival, overall survival and objective response rate as compared to vemurafenib alone,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “The preliminary results to be presented at the ESMO Congress suggest that adding atezolizumab to the combination regimen is associated both with a manageable safety profile and promising antitumor activity.”

The primary objective of the phase 1b trial is the evaluation of the safety and tolerability of the triple combination. Secondary endpoints include progression-free survival (PFS), overall survival (OS), objective response rate (ORR), best overall response, and duration of response, as well as additional exploratory objectives. Patients in the trial receive the triple combination of cobimetinib, vemurafenib, and atezolizumab after a 28-day run-in cycle of combination cobimetinib and vemurafenib. Atezolizumab is administered intravenously at 800 mg every two weeks.

As of the June 15, 2016 data cut-off, 30 patients with previously untreated BRAF V600 mutation-positive unresectable or advanced melanoma who had received at least one dose of atezolizumab were evaluable for safety. The median follow-up for safety was 3.9 months, with a range of 0.7 to 16.8 months. All-grade AEs occurring in greater than 20 percent of patients and reported as related to cobimetinib and/or vemurafenib and/or atezolizumab included elevated liver enzymes, fatigue, arthralgia, diarrhea, flu-like symptoms, photosensitivity, increased blood alkaline phosphatase, fever and pyrexia. Twelve patients had cobimetinib- and/or vemurafenib and/or atezolizumab-related grade 3/4 AEs during the triple combination period; all resolved after appropriate intervention.

Twenty-nine patients had received at least one dose of atezolizumab and undergone at least one on-treatment, post baseline tumor assessment. The ORR, a secondary endpoint, was 83 percent with 24 patients achieving a response (fifteen of which were confirmed as of the data cutoff). Three patients (10 percent) achieved complete responses and 21 patients had partial responses (72 percent). All but one subject in the trial had a reduction of tumor burden. Median duration of response and PFS were not evaluable as a result of limited follow-up time.

Immune biomarkers potentially predictive of clinical responses were evaluated in this phase 1b trial. Increases in CD8+ T cells in the tumor were observed following cobimetinib and vemurafenib treatment during the run-in period.

A pivotal placebo-controlled phase 3 trial evaluating the combination of cobimetinib, vemurafenib and atezolizumab compared to cobimetinib, vemurafenib and placebo was recently posted on ClinicalTrials.gov. Sponsored by Roche, the full title of study NCT02908672 is “A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Participants With Metastatic or Unresectable Locally Advanced Melanoma.” Exelixis expects to share additional details of this trial as they become available from its collaborator Roche.

Cobimetinib is a selective inhibitor of MEK that was discovered by Exelixis and is the subject of a worldwide collaboration agreement between Exelixis and Genentech. Cobimetinib is approved in multiple countries to treat specific forms of BRAF V600 mutation-positive unresectable or metastatic melanoma, in combination with vemurafenib. Atezolizumab is an anti-PD-L1 antibody developed by Genentech that received FDA approval to treat previously treated bladder cancer in May 2016.

Additional Cobimetinib Data Presented at the ESMO 2016 Congress

The poster discussion presentation in advanced melanoma is one of seven cobimetinib abstracts being presented at the ESMO 2016 Congress. Additional data presentations include studies of cobimetinib in combination with other therapies to treat metastatic colorectal cancer and triple-negative breast cancer and BRAF-mutant melanoma. For full logistical information on these other presentations, please see Exelixis’ ESMO announcement press release issued on August 31, 2016, available online here.

About the Cobimetinib Development Collaboration

Exelixis discovered cobimetinib internally and advanced the compound to investigational new drug (IND) status. In late 2006, Exelixis entered into a worldwide collaboration agreement with Genentech, under which Exelixis received initial upfront and milestone payments for signing the agreement and submitting the IND. Following the determination of the maximum tolerated dose in phase 1 by Exelixis, Genentech exercised its option to further develop cobimetinib.

Under the terms of the collaboration, Exelixis is entitled to an initial equal share of U.S. profits and losses, which will decrease as sales increase, and shares U.S. commercialization costs. In November 2013, Exelixis exercised its option to co-promote cobimetinib in the United States and fields 25 percent of the U.S. sales force, closely coordinating its efforts with Genentech. Outside of the United States, Exelixis is eligible to receive royalties on any sales.

Cobimetinib is now approved in multiple countries, including the United States, European Union, Switzerland, Canada, Australia and Brazil, to treat specific forms of BRAF mutation-positive unresectable or metastatic melanoma, in combination with vemurafenib. The trade name for cobimetinib is COTELLIC®. Further country approvals are anticipated in 2016 and beyond. Cobimetinib is also the subject of a clinical development program aimed at evaluating its potential in combination with a variety of investigational and approved therapies in disease settings including metastatic melanoma, triple-negative breast cancer and advanced solid tumors.

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