IMspire150
IMspire150 tested adding the immunotherapy drug atezolizumab to the two targeted pills used for BRAF-mutant melanoma; the triple combination kept the cancer from growing for longer as judged by the treating doctors, which earned it approval, but it did not help people live longer.
Overview
IMspire150 was a double-blind placebo-controlled phase 3 trial in previously untreated BRAF V600 mutation-positive unresectable or metastatic melanoma. After a 28-day run-in of vemurafenib and cobimetinib, patients continued the two targeted drugs with atezolizumab or placebo.
Investigator-assessed progression-free survival, the primary endpoint, was significantly longer with the triplet, which led to approval of atezolizumab with vemurafenib and cobimetinib in the United States in July 2020. Independent review did not confirm a significant difference, and the final overall survival analysis found no significant benefit. The trial, alongside COMBI-i, showed that layering a checkpoint inhibitor onto BRAF and MEK inhibition adds toxicity for a modest gain, and sequencing trials such as DREAMseq favour starting with immunotherapy.
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