Additional Approval of Combination Therapy with BRAFTOVI® Capsule, a BRAF Inhibitor, for the Indication of Colorectal Cancer in South Korea
- Combination therapy with Braftovi, cetuximab, and chemotherapy was approved in South Korea based on the results of clinical trial for the first-line treatment of unresectable, advanced or recurrent colorectal cancer with BRAF mutation
- Braftovi combination therapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint in a global multicenter Phase 3 clinical trial
Osaka, Japan, January 13, 2026 – Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; “Ono”) today announced that Ono Pharma Korea Co., Ltd. (Seoul, Korea; “OPKR”), a Korean subsidiary of Ono, received the additional approval for BRAFTOVI® (generic name: encorafenib) Capsule (“Braftovi”), a BRAF inhibitor, on January 9 from the Ministry of Food and Drug Safety (MFDS) in South Korea, in combination with cetuximab, an anti-human EGFR monoclonal antibody, and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAFV600Emutation.
This approval is based on the results of a global multicenter, Phase 3 BREAKWATER study (ONO-7702-03/C4221015). In the randomized Phase 3 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.
*: chemotherapy with or without bevacizumab, an anti-human VEGF monoclonal antibody
About BREAKWATER study (ONO-7702-03/C4221015)
The BREAKWATER study is a global multicenter, randomized, open-label Phase 3 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 mCRC with BRAFV600Emutation.
In the randomized Phase 3 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 mCRC with BRAFV600Emutation 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 3 part of the trial are ORR and progression-free survival PFS as assessed by a BICR. Secondary endpoints include overall survival (OS) as key secondary endpoint, and ORR and PFS both as assessed by the medical institutions, etc. Additionally, a randomized cohort set up separately from the Phase 3 part is underway to evaluate the efficacy and safety of the combination therapy with Braftovi, cetuximab, and FOLFIRI, compared with chemotherapy.
About colorectal cancer (CRC)
CRC is a malignant tumor that occurs primarily in the colon or the rectum. In South Korea, CRC is the second most common colorectal cancer with approximately 29,000 new cases diagnosed annually1) (approximately 1,926,000 cases worldwide2)), and approximately 11,000 deaths reported annually1) (approximately 904,000 deaths worldwide2)), making it the third most common cancer.
In South Korea, BRAFV600Emutation-positive patients are found in 4.7% of CRC patients (5 to 12% in the US and EU), and the prognosis is poorer than in those without the BRAFV600Emutation3). As no drugs have been approved for the first-line treatment of BRAF-mutant CRC, there is a high unmet need for this cancer and Braftovi will be a new treatment option.
- Globocan 2022: Colorectal Cancer, Korea republic, World Health Organization Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/410-korea-republic-of-fact-sheet.pdf - Globocan 2022: Colorectal Cancer, World, World Health Organization Available at:
https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf - Lee Y, Lee S, Sung JS, et al. Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project. Cancer Res Treat. 2021;53(1):123-130. doi:10.4143/crt.2020.559
About Braftovi
Braftovi is a small molecule BRAF kinase inhibitor. BRAF is an important protein kinase in the MAPK signalling pathway (RAS-RAF-MEK-ERK), which regulates several key cellular activities including proliferation, differentiation, survival, and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many types of cancers including melanoma, thyroid cancer, and CRC. Braftovi targets key enzymes in this pathway.
In South Korea, it received approval in August 2021 for the treatment of adult patients with unresectable advanced or recurrent CRC with a BRAFV600Emutation after prior therapy, in doublet combination treatment of Braftovi and cetuximab.
About the Ono Pharmaceutical Co., Ltd. and Pfizer Inc. Collaboration
In May 2017, Ono entered into the license agreement with Array BioPharma Inc. (became a subsidiary of Pfizer Inc. as of July 2019) regarding Braftovi (encorafenib), a BRAF inhibitor and Mektovi (binimetinib), a MEK inhibitor and received rights to develop and commercialize both products in Japan and South Korea.
About Ono Pharma Korea Co., Ltd. (OPKR)
OPKR is an Ono’s wholly-owned subsidiary established in December 2013. OPKR has established our own sales organization in South Korea and marketed Opdivo, an anti-PD-1 antibody/anti-neoplastic drug through our own sales organization since 2015. OPKR has been committed to developing and marketing innovative new products to meet unmet medical needs and bring them to patients in South Korea as soon as possible.