A multicenter phase II trial of encorafenib, binimetinib, and cetuximab for early relapsed stage II/III BRAF V600E -mutated colorectal cancer: TRESBIEN trial (OGSG 2101).

3567 Background: Patients with BRAF V600E -mutated colorectal cancer (CRC) who experience early recurrence during or shortly after adjuvant therapy show an extremely poor prognosis. The efficacy of BRAF-targeted triplet therapy for early relapse remains unclear. Methods: We conducted a prospective, open-label, multicenter, phase II trial evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in BRAF V600E -mutated CRC patients who relapsed during or within 6 months after completing adjuvant chemotherapy. Patients received encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m 2 once on day 1 of cycle 1, then 250 mg/m 2 once weekly until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate (ORR) by blinded independent central review. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Sample size was determined based on a threshold ORR of 6.0% and an expected ORR of 26.0% (one-sided α = 0.05, power = 0.90). Results: Between January 2022 and April 2025, 25 patients were enrolled across 14 institutions. Baseline characteristics included: median age 68 years (range, 28–81); female, n = 18 (72.0%); right-sided, n = 18 (72.0%); pStage II/III, n = 2 (8.0%)/23 (92.0%); MSI-H, n = 5 (20.0%); and prior oxaliplatin-based adjuvant chemotherapy, n = 22 (88.0%). Twenty-four patients were evaluable for efficacy. The ORR was 62.5% (95% CI, 40.6–81.2, one-sided P < 0.001), and DCR was 87.5% (95% CI, 67.6–97.3). With median follow-up time of 18.0 months, the median PFS was 7.4 months (95% CI, 4.7–10.6), and the median OS was 33.9 months (95% CI, 11.0–NE). No Grade ≥3 adverse events (≥10%) and treatment-related deaths were observed. Conclusions: The combination of encorafenib, binimetinib, and cetuximab demonstrated favorable efficacy and a manageable safety profile in patients with BRAF V600E -mutated CRC who relapsed early recurrence during or shortly after adjuvant chemotherapy. This triplet regimen can be a promising treatment strategy for this poor prognostic population. Clinical trial information: jRCTs051210152.