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ANCHOR CRC: a phase 2, open-label, single arm, multicenter study of encorafenib (ENCO), binimetinib (BINI), plus cetuximab (CETUX) in patients with previously untreated BRAF V600E-mutant metastatic colorectal cancer (mCRC)
BRAF mutations are found in up to 15% of mCRC, about 90% being V600E, and are associated with poor prognosis. There are no specific therapies approved for BRAFV600E-mutant mCRC and current available therapies lead to limited responses and short survival. ln patients with BRAF V600E-mutant mCRC, treatment with ENCO + BINI +CETUX as 2nd or 3rd line treatment has demonstrated improved outcomes compared to historical data with higher response rates in patients with fewer lines of therapy (Van Cutsem 2018). These preliminary clinical data together with previously generated preclinical data support the evaluation of this triplet combination in the 1st line setting.
This is an open-label, multicenter, single-arm, two-stage phase 2 trial in patients ≥18 years with histologically/cytologically confirmed mCRC, harboring a BRAF V600E mutation identified in tumor tissue by local assay, evidence of measurable disease per RECIST1.1, ECOG PS of O or 1, and no prior systemic therapy for metastatic disease or treatment with RAF inhibitor, MEK inhibitor, CETUX or any other anti-EGFR inhibitor. Treatment consists of oral ENCO (300 mg QD) + oral BINI (45 mg BID) + intravenous CETUX (400 mg/m2 followed by 250 mg/m2 QW x 28 wks, then 500 mg/m2 Q2W). Patients will be treated in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, or death. The primary outcome is confirmed overall response rate (cORR) based on local assessment. Secondary outcome measures include centrally assessed cORR, duration of response (DOR), time to response (TIR), progression-free survival (PFS), overall survival (OS), safety and health-related quality of life (EORTC-QLQ-C30, EQ-5D-5L and PGIC). Predictive biomarkers of activity, BRAF V600E status in circulating tumor DNA (ctDNA) and predictive significance of the microsatellite instability (MSI) status will also be investigated. Approximately 90 patients are planned to be enrolled in 10 countries worldwide and recruitment is ongoing.
NCT03693170.
