Braftovi (encorafenib)

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=10, Active, not recruiting, UNICANCER | Trial completion date: Mar 2026 --> Mar 2027

The recent approval of encorafenib, cetuximab, and FOLFOX based on the phase III BREAKWATER trial has introduced a new standard of care for the first-line treatment of BRAF V600E-mutated metastatic colorectal cancer (mCRC)...The patient then successfully underwent complete surgical resection of his primary tumor and metastatic disease with negative margins. This case highlights the importance of considering encorafenib-based therapy in select patients with BRAF V600E-mutated mCRC in the setting of compromised liver function.

P2, N=7, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | N=43 --> 7 | Trial primary completion date: Jul 2028 --> May 2026

P2, N=86, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> Feb 2026

EC+FOLFIRI demonstrated clinically meaningful and statistically significant improvements in ORR and PFS, with prolonged OS versus control in BRAF V600E-mutant mCRC. The safety profile was generally manageable, with no new safety signals. These data support EC+FOLFIRI as an additional new standard of care for patients with BRAF V600E-mutant mCRC, enabling treatment personalisation.

P2, N=43, Recruiting, Northwestern University | Trial completion date: Jul 2028 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

This functional precision oncology platform integrates multi-omics and immune co-culture to uncover RNF43 mutation as a dual biomarker for targeted therapy sensitivity and tumor immunogenicity in BRAFV600E-mutant CRC. Our findings provide mechanistic rationale for combining BRAF/EGFR inhibition with immunotherapy to overcome drug resistance and improve outcomes in this aggressive subtype.

This study assessed the cost-effectiveness of encorafenib plus cetuximab (EC) and EC combined with mFOLFOX6 versus standard of care (SOC) as first-line treatment for BRAF V600E-mutant metastatic colorectal cancer from a Chinese healthcare perspective...At this threshold, SOC had a 95.43% probability of being cost-effective against EC, and 99.64% against EC plus mFOLFOX6. We conclude that neither EC nor EC plus mFOLFOX6 is cost-effective in China at current prices, suggesting the price negotiations would be necessary to improve their economic value.

We describe the case of a man in his 60s with metastatic melanoma on encorafenib/binimetinib and nivolumab/relatlimab, with a history of immune checkpoint inhibitor (ICI)-induced acute interstitial nephritis, who presented with acute-onset nausea, vomiting and profuse watery diarrhoea. His symptoms persisted despite discontinuation of Braftovi-Mektovi (BRAF-MEK) therapy and required escalation of corticosteroid therapy and budesonide initiation. This case highlights the diagnostic challenges of differentiating ICI-mediated colitis from adverse events of targeted therapy and underscores the importance of endoscopic and histological confirmation in guiding treatment.

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.