Braftovi (encorafenib)

P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Outcomes following progression on chemotherapy and MAPK-targeted therapy with Encorafenib plus Cetuximab remain poor, highlighting an unmet need for effective later-line treatments. We discuss the mechanistic framework by which a subset of BRAFV600E-mutant MSS mCRC may respond to immune checkpoint inhibition through an inflamed immune microenvironment driven by constitutive MAPK signalling. This case illustrates the interplay between tumour-agnostic biomarkers such as TMB-high and tumour-specific context, and highlights the value of longitudinal genomic profiling, including ctDNA, to identify resistance mechanisms and guide treatment selection.

P2, N=25, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Active, not recruiting --> Recruiting

P2, N=25, Not yet recruiting, Vall d'Hebron Institute of Oncology

P4, N=46, Recruiting, Pfizer | N=71 --> 46

This study investigates the synergistic effects of capivasertib, an Akt pathway inhibitor, in combination with B-Raf inhibitors (vemurafenib and encorafenib) in B-Raf-mutated melanoma models. Systemic toxicity analyses revealed no significant changes in body weight or serum markers of pancreatic, kidney, or liver function. These findings establish capivasertib and B-Raf inhibitor combinations as a safe and effective strategy for overcoming resistance B-Raf-mutated melanoma, providing new insights into the potential of dual pathway targeting.

P4, N=0, Withdrawn, SRH Wald-Klinikum Gera GmbH | N=101 --> 0 | Not yet recruiting --> Withdrawn

P2, N=25, Active, not recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Recruiting --> Active, not recruiting

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.

P2, N=24, Active, not recruiting, Providence Health & Services | Trial completion date: Jan 2027 --> Dec 2028 | Trial primary completion date: Jan 2026 --> Dec 2027

P=N/A, N=50, Active, not recruiting, Pierre Fabre Ltd | Recruiting --> Active, not recruiting

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.