BRAF V600K

Our study demonstrates the superiority of ctDNA harboring melanoma specific mutations over LDH and S100 in identifying patients at risk for recurrence in early melanoma stages in a single center cohort of melanoma patients. Future prospective trials are warranted to confirm this.

These results indicate that rare BRAF mutations can modify BRAF kinase activity including a subset of mutations outside but close to codon 600. Molecular approaches able to detect rare BRAF mutations could identify additional melanoma cases eligible for therapies with BRAF/MEK inhibitors.

P1, N=6, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2027

P1, N=91, Terminated, Deciphera Pharmaceuticals, LLC | Phase classification: P1/2 --> P1 | N=144 --> 91 | Trial completion date: Aug 2028 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2027 --> Mar 2026; Trial terminated due to business decision, not based on any safety or efficacy concerns.

P2, N=10, Active, not recruiting, UNICANCER | Trial completion date: Apr 2029 --> Mar 2026 | Trial primary completion date: Apr 2025 --> Mar 2026

P2, N=280, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

Using a longitudinal time-to-event modeling framework, this proof-of-concept study demonstrates the feasibility of kinetic ctDNA-based risk estimation throughout systemic treatment. Both single-point ctDNA measures and their kinetics may serve as indicators of future disease progression.

P2, N=38, Terminated, Pfizer | Active, not recruiting --> Terminated; Study terminated due to inability to recruit the target number of patients. There were no safety and/or efficacy concerns involved in the decision to stop enrollment.

P3, N=257, Active, not recruiting, Pfizer | Trial completion date: Mar 2026 --> Aug 2026

P1, N=2, Active, not recruiting, Richard Wu | Trial completion date: Dec 2025 --> Dec 2026

P1/2, N=16, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 16 | Trial completion date: Nov 2025 --> Jan 2027

The greatest benefits of encorafenib plus binimetinib were observed in patients with evidence of high TMB and/or tumor immune infiltration, suggesting potential immune contributions to efficacy, which were not observed with vemurafenib. BRAF V600 detectability in ctDNA appears to have utility as a marker of prognosis and response in this population.