Braftovi (encorafenib)

We report here a patient on encorafenib who developed numerous new pigmented lesions within 3 weeks of therapy...This case underscores that BRAF inhibition may enhance PRAME expression in benign melanocytic nevi, potentially through mechanisms involving mitogen-activated protein kinase (MAPK) activation, altered Erk phosphorylation, or disruption of retinoic acid (RA) signaling. This case also brings awareness to the potential of medication-induced PRAME expression and encourages both dermatologists and dermatopathologists to avoid overdiagnosis as PRAME continues to gain prominence as a diagnostic biomarker.

Targeted inhibition with the oral BRAF inhibitor encorafenib, combined with intravenous cetuximab targeting epithelial growth factor receptor (EGFR) and standard chemotherapy FOLFOX, has improved outcomes and received FDA approval in 2025 based on results from the phase III BREAKWATER trial...This case demonstrates that rectal and nasogastric administration of encorafenib is feasible, achieves therapeutic plasma concentrations, and induces objective and clinical remission in context of FOLFOX+EC. Short-term safety appeared manageable, though increased infection risk cannot be excluded.

Trastuzumab-based combinations and HER2-selective tyrosine kinase inhibitors such as tucatinib have demonstrated durable responses and favorable safety profiles in heavily pretreated patients. This review summarizes current evidence from pivotal phase II and III clinical trials, translational studies, and real-world data evaluating EGFR-, BRAF-, and HER2-directed therapies in colorectal cancer. Particular emphasis is placed on biomarker-guided patient selection, mechanisms of resistance, and emerging combination strategies that continue to refine precision oncology approaches in mCRC.

In a compound screen on melanoma cells, we identified FX-11 as one of the compounds inhibiting the growth of sensitive and Encorafenib/Binimetinib-resistant 624Mel and Wm3248 melanoma cells. Taken together, we provide evidence that FX-11 inhibits the growth of melanoma cells, including drug-resistant ones, through an AMPK-dependent mechanism by acting as a mitochondrial uncoupler. Our data do not support that FX-11 acts as an LDH inhibitor.

Combination therapy of encorafenib plus binimetinib for unresectable BRAF V600-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

P1/2, N=101, Completed, Erasca, Inc. | Active, not recruiting --> Completed

P2, N=25, Recruiting, Vall d'Hebron Institute of Oncology | Not yet recruiting --> Recruiting

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

P2, N=84, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Sep 2026 | Trial primary completion date: Feb 2026 --> Sep 2026