FDA Approves Combination Treatment for Advanced Melanoma
The U.S. Food and Drug Administration has approved atezolizumab plus cobimetinib and vemurafenib for treatment of BRAF V600 mutation-positive advanced melanoma. Studies show the combination treatment prolonged patients’ lives by 15 months without disease worsening.
A new combination treatment from Genentech will be joining the skin cancer market with the recent approval by the U.S. Food and Drug Administration (FDA) for atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for treatment of BRAF V600 mutation-positive advanced melanoma. The FDA granted the supplemental Biologics License Application for atezolizumab under Priority Review.
The decision by the FDA is backed by results from the IMspire150 study, a phase 3, randomized, double-blind, placebo-controlled trial that evaluated the safety and efficacy of atezolizumab used in combination with cobimetinib and vemurafenib versus placebo plus cobimetinib and vemurafenib in 513 previously untreated BRAF V600 mutation-positive advanced or metastatic melanoma patients.
The study’s primary endpoint was investigator-assessed progression-free survival (PFS) and secondary endpoints were PFS by an independent review committee, objective response rate, overall survival, duration of response, as well as other various pharmacokinetic and safety measures.
Results of the study demonstrated atezolizumab plus cobimetinib and vemurafenib aided in prolonging patients’ lives without disease worsening or death (PFS) versus placebo plus cobimetinib and vemurafenib (median PFS 15.1 months compared to10.6 months; hazard ratio=0.78; confidence interval: 0.63-0.97; P=0.025).
"When receiving a cancer immunotherapy combined with targeted therapies, patients with BRAF V600 mutation-positive advanced melanoma were able to live for more than 15 months without their disease worsening," says Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech. "Today's FDA approval of this Tecentriq combination represents an important step forward for many patients living with advanced melanoma."
The combination’s safety profile was also consistent with previously reported safety data of the individual drugs. The most common adverse reactions for atezolizumab plus cobimetinib and vemurafenib included rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
Atezolizumab is a monoclonal antibody that binds to the protein PD-L1 that is found on tumor cells and tumor-infiltrating immune cells, and then blocks PD-L1’s interaction with receptors PD-1 and B7.1, thus possibly enabling the re-activation of T cells.
Cobimetinib inhibits dual-specificity MEK1/2 protein kinases, which are attributed to helping control cell survival and growth. The drug is already approved in the U.S. and other countries to be used in combination with vemurafenib to treat metastatic melanoma with a BRAF V600 mutation that is not resectable.
Vemurafenib, the first drug approved in its class, inhibits some mutated forms of BRAF, which have been known to cause irregular signaling in cancer cells later leading to tumor growth.