TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated:...in combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

This review covers the efficacy and safety of atezolizumab, cobimetinib and vemurafenib for patients with advanced or metastatic BRAF mutant melanoma….Atezolizumab plus cobimetinib and vemurafenib showed superior progression-free survival in metastatic melanoma compared to cobimetinib and vemurafenib alone. Triplet therapy might be an option in situations of urgent need for disease control, when oncologists choose BRAF/MEK inhibition over immune checkpoint inhibition as first line treatment.

The addition of atezolizumab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly increased progression-free survival in patients with BRAFV600 mutation-positive advanced melanoma.

...Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival or newly obtained) through use of a clinical mutation test approved by the local health authority...

Intracranial objective response rate was 42% (95% CI 29-54) by IRC assessment in the BRAFV600 mutation-positive cohort….Atezolizumab plus vemurafenib and cobimetinib provided intracranial activity in patients with BRAFV600-mutated melanoma with CNS metastases.

Intracranial ORR was 42% by IRC and 51% by investigator (BOR concordance: 68%). In pts on corticosteroids and/or symptomatic at baseline, ORR was 58%, DOR was 10.2 mo, and PFS was 7.2 mo by investigator; in asymptomatic pts, ORR was 46%, DOR was 5.7 mo, and PFS was 5.5 mo. Addition of A to C + V provides promising intracranial activity in pts with BRAFV600-mutated melanoma with CNS mets, particularly in those receiving corticosteroids and/or in symptomatic pts.

The phase III IMspire150 study (NCT02908672) demonstrated improved progression-free survival with first-line A vs placebo (P) combined with V+C in patients (pts) with BRAF V600 mutation–positive advanced melanoma...514 pts were randomized 1:1 to A+V+C or P+V+C. Pts received V+C from cycle 1; A or P was added from cycle 2 onward. Incidence (overall and by cycle), time to onset/resolution, and recurrence of select AESIs were evaluated in the safety population (A+V+C, n=230; P+V+C, n=281)...These data indicate that key AESIs with A+V+C occur early during treatment; are manageable, with resolution times similar to those with V+C; and have low to moderate risk of recurrence. Recurrent AESIs are generally mild to moderate in severity with no evidence of cumulative effect.

This phase Ib study (ClinicalTrials.gov, number NCT01656642 ) evaluated the safety and anti-tumor activity of combining atezolizumab (anti-PD-L1) with vemurafenib (BRAF inhibitor), or cobimetinib (MEK inhibitor) + vemurafenib, in patients with BRAFV600-mutated metastatic melanoma...The confirmed objective response rate was 71.8% (95% confidence interval 55.1-85.0). The estimated median duration of response was 17.4 months (95% confidence interval 10.6-25.3).