ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer

by Selleckchem | May 17 2023

Purpose: The positive BEACON colorectal cancer (CRC) safety lead-in, evaluating encorafenib + cetuximab + binimetinib in previously treated patients with BRAFV600E-mutated metastatic CRC (mCRC), prompted the design of the phase II ANCHOR CRC study . ANCHOR CRC aimed to evaluate efficacy, safety, and quality of life with first-line encorafenib + binimetinib + cetuximab in BRAFV600E-mutated mCRC.

Methods: In this multicenter, open-label, single-arm study, patients with BRAFV600E-mutated mCRC received oral encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m2 once on Day 1 of Cycle 1, then 250 mg/m2 once weekly for the first seven cycles, and 500 mg/m2 once on Days 1 and 15 from Cycle 8 onward. The primary end point was locally assessed confirmed objective response rate (cORR), and secondary end points included centrally assessed cORR, progression-free survival, overall survival (OS), quality of life, and safety and tolerability.

Results: Among 95 patients, the locally assessed cORR was 47.4% (95% CI, 37.0 to 57.9) with all partial responses. Since the lower limit of the 95% CI exceeded 30%, the primary end point was met. With a median follow-up duration of 20.1 months, the median progression-free survival on the basis of local assessments was 5.8 months and the median OS was 18.3 months. Treatment was well tolerated, with no unexpected toxicities. Using Patient Global Impression of Changes, substantial improvement in symptoms was consistently reported in ≥ 30% of patients from Cycle 3 to Cycle 10.

Conclusion: The ANCHOR CRC study showed that the scientifically driven combination of encorafenib + binimetinib + cetuximab was active in the first-line setting of BRAFV600E-mutated mCRC with a manageable safety profile.

Comments：

The ANCHOR CRC study was designed to evaluate the efficacy, safety, and quality of life with first-line encorafenib + binimetinib + cetuximab in patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC). This was a multicenter, open-label, single-arm study, in which patients received oral encorafenib, binimetinib, and intravenous cetuximab. The primary endpoint was locally assessed confirmed objective response rate (cORR), and secondary endpoints included centrally assessed cORR, progression-free survival, overall survival (OS), quality of life, and safety and tolerability.

The study showed that among the 95 patients, the locally assessed cORR was 47.4%, with all partial responses. The primary endpoint was met, as the lower limit of the 95% CI exceeded 30%. The median progression-free survival was 5.8 months, and the median OS was 18.3 months, with a median follow-up duration of 20.1 months. Treatment was well tolerated, with no unexpected toxicities, and patients consistently reported substantial improvement in symptoms using Patient Global Impression of Changes from Cycle 3 to Cycle 10.

Overall, the ANCHOR CRC study demonstrated that the combination of encorafenib + binimetinib + cetuximab was active in the first-line setting of BRAFV600E-mutated mCRC, with a manageable safety profile.