Background: IMspire150 aimed to judge first-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAFV600 mutation-positive advanced or metastatic melanoma.
Methods: IMspire150 would be a randomised, double-blind, placebo-controlled phase 3 study done at 112 institutes in 20 countries. Patients with unresectable stage IIIc-IV, BRAFV600 mutation-positive melanoma were at random assigned 1:1 to twenty-eight-day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo, vemurafenib, and cobimetinib (control group). In cycle 1, all patients received vemurafenib and cobimetinib only atezolizumab placebo was added from cycle 2 forward. Randomisation was stratified by lactate dehydrogenase concentration and geographical region. Blinding for atezolizumab was achieved by way of the same intravenous placebo, and blinding for vemurafenib was achieved using a placebo tablet. The main effects were investigator-assessed progression-free survival. This trial (ClinicalTrials.gov, NCT02908672) is ongoing but no more recruiting patients.
Findings: Between Jan 13, 2017, and April 26, 2018, 777 patients were screened and 514 were enrolled and at random allotted to the atezolizumab group (n=256) or control group (n=258). In a median follow-from 18?¡è9 several weeks (IQR 10?¡è4-23?¡è8), progression-free survival as assessed through the study investigator was considerably prolonged with atezolizumab versus control (15?¡è1 versus 10?¡è6 several weeks hazard ratio [HR] 0?¡è78 95% CI 0?¡è63-0?¡è97 p=0?¡è025). Common treatment-related adverse occasions (>30%) within the atezolizumab and control groups were bloodstream creatinine phosphokinase elevated (51?¡è3% versus 44?¡è8%), diarrhoea (42?¡è2% versus 46?¡è6%), rash (40?¡è9%, both groups), arthralgia (39?¡è1% versus 28?¡è1%), pyrexia (38?¡è7% versus 26?¡è0%), alanine aminotransferase elevated (33?¡è9% versus 22?¡è8%), and lipase elevated (32?¡è2% versus 27?¡è4%) 13% of patients within the atezolizumab group and 16% within the control group stopped all treatment due to adverse occasions.
Interpretation: Adding atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and considerably elevated progression-free survival in patients with BRAFV600 mutation-positive advanced melanoma.