Cotellic (cobimetinib)

KSR1 knockdown did not substantially affect ppERK responses to Type I½ RAF inhibitor (Encorafenib) in both cell types, whereas ppERK sensitivity slightly decreased for Type II RAFi (TAK-632) in MCF7 cells, aligning with simulations. The efficacy of MEKi (Cobimetinib) slightly increased in MCF7 cells following KSR1 knockdown but slightly decreased in PSN1 cells where higher MEKi concentrations were required to suppress ERK signaling, as predicted by the model. Our computational models predict, and experiments validate that in RAS-mutant cells, two conformation-specific RAF inhibitors used in combination suppress the ERK pathway more effectively than a combination of MEK and RAF inhibitors irrespective of KSR1 levels.

In the absence of head-to-head trials comparing 1L nivolumab plus relatlimab (NIVO+RELA) to BRAF/MEK inhibitors, we compared its efficacy to dabrafenib+trametinib (DAB+TRAM), encorafenib+binimetinib (ENCO+BINI), vemurafenib+cobimetinib (VEM+COBI) and atezolizumab (ATEZO)+VEM+COBI using matching-adjusted indirect comparisons (MAICs)...These MAICs suggest that 1L dual IO therapy with NIVO+RELA confers a long-term OS advantage in BRAF-mutant advanced melanoma compared with BRAF/MEK inhibitor combinations despite lower ORR, consistent with prior evidence for 1L NIVO+IPI in this setting. As unanchored analyses, potential residual confounding remains, and results should be interpreted cautiously.

P1, N=42, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1/2, N=50, Recruiting, Universita' Degli Studi Di Perugia | Not yet recruiting --> Recruiting

P1, N=70, Completed, F. Hoffmann-La Roche AG | Recruiting --> Completed

She was initially treated with Vemurafenib and Cobimetinib, achieving complete remission. However, due to cumulative toxicities, therapy was switched to Encorafenib and Binimetinib in February 2023...Management included Binimetinib dose reduction and topical ketorolac, resulting in initial improvement, although the CME recurred several months later...The patient ultimately began immunotherapy with Nivolumab and Ipilimumab, but died in February 2024 due to refractory abdominal septic shock. This case highlights the importance of early ophthalmologic monitoring and interdisciplinary collaboration in patients receiving MEK inhibitors.

P2, N=720, Recruiting, Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 --> Dec 2026

P2, N=45, Recruiting, Hanmi Pharmaceutical Company Limited

Therefore, this study aimed to examine the protein composition of the secretome of cells resistant to vemurafenib (a BRAF inhibitor) and cobimetinib (a MEK inhibitor) and to compare it with that of nonresistant cells. Proteins secreted by resistant melanoma cells can undoubtedly influence the surrounding microenvironment in a way that promotes the formation of a pro-tumor niche. Among the proteins secreted in significantly higher amounts by resistant cells (compared to the control group), which may be potential biomarkers or therapeutic targets in melanoma, plasminogen activator inhibitor 1, thymosin beta-4, clusterin, interleukin-6, superoxide dismutase, and selected matrix metalloproteinases can be distinguished.

P1, N=70, Recruiting, F. Hoffmann-La Roche AG | -> Recruiting | Phase classification: PN/A --> P1

P2, N=29, Active, not recruiting, University of Utah | Trial primary completion date: Jan 2026 --> Apr 2025

P1, N=65, Active, not recruiting, Genentech, Inc. | Trial completion date: Dec 2025 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Jun 2027