Updated data from Genentech’s Phase 3 clinical trial of patients with BRAF V600 mutation-positive advanced melanoma treated with cobimetinib (an investigational MEK inhibitor) in combination with Zelboraf® (vemurafenib) show that co-treated patients have a significantly longer progression-free survival than patients treated with Zelboraf only. This data will be considered by the Food and Drug Administration in the coming months when the FDA meets to discuss Genentech’s new drug application for cobimetinib in combination with Zelboraf. The European Medicines Agency will also make a decision on Roche’s marketing of cobimetinib by the end of the year.
“The combination of cobimetinib and Zelboraf extended the time people lived without their disease getting worse to a year,” said Sandra Horning, MD, chief medical officer and head of Global Product Development, in a news release from Genentech, a member of the Roche group. “These results are exciting because they underscore the importance of combining medicines that target the signals, which cause about half of all melanomas to grow.”
In an exclusive interview with BioNews, Josina Reddy, M.D., Ph.D., Group Medical Director, Product Development, Genentech commented on her thoughts on the potential of combination therapies in cancer treatment, “Studies have shown that when tumors are blocked in one pathway, they could find another to continue growing and spreading, so combinations of medicines using different pathways and approaches are important approaches to help people who have serious, difficult to treat diseases. We have more than 30 ongoing studies evaluating combinations of cancer medicines, including targeted therapies, immunotherapies, and chemotherapy. In the case of cobimetinib and Zelboraf, the data support the hypothesis that targeting both MEK and mutant BRAF in the MAPK signaling pathway can help delay disease progression in people with BRAF V600 mutation-positive advanced melanoma. In melanoma, we also have an ongoing Phase Ib study with cobimetinib, Zelboraf and atezolizumab, our anti-PDL1 cancer immunotherapy.”
Newly released data show that median progression-free survival was over a year (12.3 months) for patients treated with cobimetinib and Zelboraf, compared to only 7.2 months for patients treated with Zelboraf alone. These patients were part of the Phase 3 coBRIM study, which evaluated 495 patients treated with 60 mg once daily of cobimetinib in combination with 960 mg twice daily of Zelboraf, or 960 mg twice daily of Zelboraf alone.
As an added benefit, co-treated patients experienced a higher objective response rate of 70%, compared to 50% for Zelboraf-only treated patients. The complete response rate was raised 6 percentage points in co-treated patients after a year of treatment, as these patients had a partial response with less than a year of treatment. Both groups showed safety profiles similar to those of previous clinical trials.
New data from clinical trials is also being released. In the Phase Ib BRIM7 study, patients treated with cobimetinib and Zelboraf were alive for a median of two years after treatment, with 61% of patients alive for more than two years. Again, safety was similar as before for both treatments.
“The approval of cobimetinib in combination with Zelboraf is anticipated by August 11. We won’t know until it has been approved when it will be available, but will work to make the medicines available quickly. We’re committed to making sure the people who need our medicines can get them and are also working to ensure our patient assistance programs are available at approval”, Dr. Reddy told BioNews.
The data is being presented by representatives from Genentech during the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) held in Chicago May 29th to June 2nd. Dr. James Larkin, FRCP, from The Royal Marsden Hospital in London, is presenting the coBRIM study data during an oral session. Dr. Anna Pavlick, from New York University Medical Center, is presenting a poster presentation on the BRIM7 data.