Cobimetinib and vemurafenib plus atezolizumab

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

At a median follow-up of 19 months, the primary investigator median PFS was 15 months (95% CI, 11.4−18.4) in the atezolizumab arm and 11 months (95% CI, 9.3−12.7) in the placebo arm (HR, 0.78; 95% CI, 0.63−0.97; P = .0249).

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

An IRC assessment of the triplet therapy found a PFS of 16 months (95% CI, 11.3−18.5), compared with 12 months in the control arm (95% CI, 10.8−14.7) (HR, 0.85; 95% CI, 0.67−1.07).

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

Objective response rates and complete responses were similar between the treatment groups.

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

Data are not mature for OS.

A double-blind, placebo-controlled, multicenter trial (IMspire150 [NCT02908672]) included 514 patients with unresectable stage IIIC or metastatic melanoma and BRAF V600 pathogenic variants. Patients were randomly assigned (1:1) to receive first-line therapy with cobimetinib plus vemurafenib with either atezolizumab or placebo.[35] Eligibility criteria included ECOG PS scores of 0 to 1, measurable disease, and no previous systemic treatment for metastatic melanoma. Patients with untreated or actively progressing brain metastases or a history of serious autoimmune disease were excluded. Previous adjuvant therapy was allowed (14% of patients).After all patients in both arms received a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab (840 mg IV every 2 weeks) or placebo in addition to the combination BRAF-MEK inhibitor therapy. The primary efficacy end point was investigator-assessed PFS per RECIST 1.1 criteria.

Serious adverse events and treatment discontinuations because of toxicity were similar between the arms. Grade 5 adverse events occurred in seven patients in each arm. Two patients with hepatic failure in the atezolizumab group and one patient with pulmonary hemorrhage in the control group were considered treatment related.