Cobimetinib plus atezolizumab in BRAF wild-type melanoma: primary results from the randomized phase III IMspire170 study.

Background: Emerging data suggest that the combination of MEK inhibitors and immunotherapeutic agents may result in improved efficacy in melanoma. We evaluated whether combining MEK inhibition and immune checkpoint inhibition was more efficacious than immune checkpoint inhibition alone in patients with previously untreated BRAF wild-type advanced melanoma.

Patients And Methods: IMspire170 was an international, randomized, open-label, phase III study.

Extended 5-Year Follow-up Results of a Phase Ib Study (BRIM7) of Vemurafenib and Cobimetinib in -Mutant Melanoma.

Purpose: To report the 5-year overall survival (OS) landmark and the long-term safety profile of vemurafenib plus cobimetinib (BRAF plus MEK inhibition, respectively) in the BRIM7 study.

Patients And Methods: This phase Ib, dose-finding, and expansion study evaluated combination treatment with vemurafenib and cobimetinib in two cohorts of patients with advanced -mutated melanoma: patients who were BRAF inhibitor (BRAFi)-naïve ( = 63) or patients who had progressed on prior treatment with BRAFi monotherapy [vemurafenib monotherapy-progressive disease (PD); = 66]. Patients in the dose-escalation phase received vemurafenib at 720 or 960 mg twice daily in combination with cobimetinib at 60, 80, or 100 mg/d for 14 days on/14 days off, 21 days on/7 days off, or continuously.

Spatial power spectral density estimation using a Welch coprime sensor array processor.

A coprime sensor array (CSA) is a sparse array geometry that interleaves two spatially undersampled uniform linear arrays (ULAs) with coprime undersampling factors. The CSA product processor achieves an asymptotically unbiased spatial power spectral density (PSD) estimate using far fewer sensors than a conventional ULA beamformer, but at the expense of increased sidelobes and variance. Nonstationary underwater sonar environments often preclude increasing the number of snapshots required to achieve a desirable PSD variance.

Genomic Features of Exceptional Response in Vemurafenib ± Cobimetinib-treated Patients with -mutated Metastatic Melanoma.

Purpose: Previous investigations identified transcriptional signatures associated with innate resistance to anti-programmed cell death protein 1 therapy in melanoma. This analysis aimed to increase understanding of the role of baseline genetic features in the variability of response to BRAF and MEK inhibitor therapy for -mutated metastatic melanoma.

Patients And Methods: This exploratory analysis compared genomic features, using whole-exome and RNA sequencing, of baseline tumors from patients who had complete response versus rapid progression (disease progression at first postbaseline assessment) on treatment with cobimetinib combined with vemurafenib or vemurafenib alone.

Effects of Molecular Heterogeneity on Survival of Patients With -Mutated Melanoma Treated With Vemurafenib With or Without Cobimetinib in the coBRIM Study.

Purpose: The treatment of advanced -mutated melanomas with BRAF inhibitors (BRAFi) has improved survival, but the efficacy of BRAFi varies among individuals and the development of acquired resistance to BRAFi through reactivation of mitogen-activated protein kinase (MAPK) signaling is common. We performed an exploratory, retrospective analysis to investigate the effects of allelic balance, coexisting oncogene mutations, cell proliferation signaling levels, and loss of PTEN expression on progression-free survival (PFS) in patients in the phase III coBRIM study, which compared the combination of the MEK inhibitor cobimetinib with the BRAFi vemurafenib versus vemurafenib as monotherapy.

Methods: Baseline tumor samples from the intention-to-treat population were analyzed by targeted deep sequencing at a median coverage of 3,600× and by immunohistochemistry for cell proliferation markers, , and PTEN.