Abstract 440TiP
Background
The BRAF V600E mutation accounts for approximately 5% of colorectal cancer (CRC) cases and is an extremely poor prognostic factor. There are no clear recommendations for patients with early recurrent BRAF V600E-mutated CRC, during or after adjuvant chemotherapy. Recently, triplet therapy of encorafenib, binimetinib, and cetuximab, resulted in significantly longer overall survival and a higher response rate than standard chemotherapy in patients with previously treated metastatic CRC with the BRAF V600E mutation (Kopetz S, N Engl J Med. 2019.). Furthermore, in first-line treatment for BRAF V600E-mutated CRC, triplet therapy showed a promising response rate and disease control rate (Cutsem EV, Ann Oncol. 2021). These results suggest that triplet therapy may be effective even in early recurrent BRAF V600E-mutated CRC during or after adjuvant chemotherapy.
Trial design
The TRESBIEN study is an open-label, multicenter, single-arm phase II study designed to evaluate whether encorafenib, binimetinib, and cetuximab are effective for patients with early recurrent BRAF V600E-mutated CRC during or after adjuvant chemotherapy (jRCTs051210152). The main inclusion criteria were BRAF V600E- mutated stage II/III colorectal adenocarcinoma after radical resection, recurrence during or within six months of adjuvant chemotherapy with measurable lesions, no prior treatment with encorafenib, binimetinib, or cetuximab, age ≥ 20 years, ECOG PS 0 to 2, with adequate organ function. Patients will receive encorafenib, binimetinib, and cetuximab. The primary endpoint was objective response rate. To achieve 90% power to show a significant response benefit with a one-sided alpha level of 0.05, assuming a threshold objective response rate of 6.0% and an expected value of at least 26.0%, we estimated that 25 patients were required. The secondary endpoints included overall survival, progression-free survival, disease control rate, duration of response, time to treatment failure, and safety. This is the first study to investigate whether triplet therapy combined with encorafenib, binimetinib, and cetuximab is effective for the treatment of early recurrent BRAF V600E-mutated CRC. The first patient was enrolled in January 2022.
Clinical trial identification
jRCTs051210152.
Editorial acknowledgement
Legal entity responsible for the study
Osaka Gastrointestinal cancer chemotherapy Study Group (OGSG).
Funding
Ono Pharmaceutical Co., Ltd.
Disclosure
S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd, Taiho Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd.; Financial Interests, Institutional, Research Grant: Daiichi Sankyo Co. Ltd. H. Satake: Financial Interests, Personal, Invited Speaker: Bayer Co., Ltd., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd., Yakult Honsha Co., Ltd.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sanofi. S. Mitani: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co.; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co.. D. Sakai: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical Co., Ltd.Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd; Financial Interests, Institutional, Research Grant: daiichi sankyo co. ltd, Eli Lilly, Chugai Pharmaceutical Co., Ltd., ONO Pharmaceutical Co., Ltd, yakult honsha co. ltd. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Lecture: Glaxo Smith Kline K.K, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol-Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd, Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd.. T. Kato: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.Chugai Pharmaceutical Co., Ltd.. T. Satoh: Financial Interests, Personal, Invited Speaker, invited speaker and advisory: Ono Pharmaceutical, Daiichi-Sankyo; Financial Interests, Personal, Invited Speaker, Invited speaer and adovisory: Bristol-Myers; Financial Interests, Personal, Invited Speaker, Invited speaker and advisory: Elli-Lilly, Yakult-Honsha; Financial Interests, Personal, Invited Speaker: Chugai Pharmazeutical, Merck-Biopharm, Takeda, Taiho; Financial Interests, Personal, Advisory Board: Takara-Bio; Financial Interests, Institutional, Invited Speaker: Merck-Biopharm, Bristol-Myers; Financial Interests, Institutional, Invited Speaker, Research Grant and Endorsed Department: Ono Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha; Financial Interests, Institutional, Invited Speaker, Research Grant: Elli-Lilly, Daiichi-Sankyo, Parexell, Giliad, Taiho, Hutch-Med. Y. Kagawa: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K. All other authors have declared no conflicts of interest.