Ono Pharma Receives Supplemental Approval in Japan for combination therapy with Braftovi (encorafenib) capsule, a BRAF Inhibitor, for colorectal cancer

Ono Pharmaceutical Co., Ltd. announced that they received  supplemental approval in Japan for Braftovi  (encorafenib) capsule in combination with cetuximab, an anti-human EGFR monoclonal antibody, and chemotherapy for the indication of unresectable, advanced or recurrent colorectal cancer (CRC) with BRAF mutation.

This approval is based on the results of a global multicenter, Phase III BREAKWATER study (ONO-7702-03/C4221015). In the randomized Phase III part of the trial, the patients who received Braftovi in combination with cetuximab and FOLFOX (5-FU/levoleucovorin/oxaliplatin) (Braftovi combination therapy arm) demonstrated a statistically significant and clinically meaningful improvement in the objective response rate (ORR) assessed by a blinded independent central review (BICR), one of the primary endpoints, compared with the chemotherapy arm (60.9% vs 40.0%, p = 0.0008). In addition, the Braftovi combination therapy arm demonstrated a statistically significant and clinically meaningful prolongation in the progression-free survival (PFS) assessed by BICR, the other primary endpoint, compared with the chemotherapy arm (median PFS: 12.8 months vs 7.1 months, hazard ratio = 0.53; 95% confidence interval: 0.407 to 0.677; p < 0.0001). The safety profile of Braftovi combination therapy arm in the trial was consistent with the known safety profile of each drug, and no new safety signals identified.

The BREAKWATER study is a global multicenter, randomized, open-label Phase III trial evaluating the efficacy and safety of the combination of Braftovi with cetuximab and chemotherapy (FOLFOX [5-FU/levoleucovorin/oxaliplatin] or FOLFIRI [5-FU/levoleucovorin/irinotecan]) compared with chemotherapy in patients with unresectable advanced or recurrent CRC with BRAFV600E mutation. In the randomized Phase III part of the trial, the efficacy and safety of Braftovi in combination with cetuximab and FOLFOX was evaluated in the first-line treatment of unresectable advanced or recurrent CRC with BRAFV600E mutation compared with chemotherapy. Patients received 300 mg of Braftovi once daily, cetuximab once every 2 weeks, and FOLFOX once every 2 weeks until disease progression or safety concerns. The primary endpoints of the randomized Phase III part of the trial are objective response rate (ORR) and progression-free survival (PFS) as assessed by a blinded independent central review (BICR). Secondary endpoints include overall survival (OS), and ORR and PFS both as assessed by the medical institutions, etc. Additionally, a cohort set up separately from the Phase III part is underway to evaluate the efficacy and safety of the combination therapy with Braftovi, cetuximab, and FOLFIRI, compared with chemotherapy.