Braftovi (encorafenib)

P=N/A, N=82, Completed, Novartis Pharmaceuticals

P2, N=7, Terminated, Northwestern University | Trial completion date: Jul 2030 --> Apr 2026 | Active, not recruiting --> Terminated | Trial primary completion date: May 2026 --> Oct 2025; The study was closed due to accrual.

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=45 --> 28 | Trial completion date: Jul 2028 --> Jun 2029 | Trial primary completion date: Apr 2028 --> May 2026

BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization...dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC.

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.