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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

1986 - BIG BANG study: A Multicenter Phase II Study of the MEK Inhibitor Binimetinib + BRAF Inhibitor Encorafenib + Anti-EGFR Antibody Cetuximab in Patients with BRAF Non-V600E Mutated Metastatic Colorectal Cancer (EPOC 1703)

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Cytotoxic Therapy;  Targeted Therapy;  Immunotherapy

Tumour Site

Colon and Rectal Cancer

Presenters

Daisuke Kotani

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

D. Kotani1, H. Bando1, T. Masuishi2, Y. Komatsu3, K. Yamaguchi4, T.E. Nakajima5, T. Satoh6, T. Nishina7, T. Esaki8, S. Nomura9, S. Sakamoto9, S. Iida10, S. Matsuda9, M. Yonemura10, N. Fuse10, A. Sato10, S. Fujii11, H. Ebi12, A. Ohtsu1, T. Yoshino1

Author affiliations

  • 1 Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Clinical Oncology, Aichi Cancer Center Hospital, 464-8681 - Nagoya/JP
  • 3 Cancer Chemotherapy, Hokakido University Cancer Center, Sapporo/JP
  • 4 Department Of Gastroenterology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 5 Department Of Clinical Oncology, St Marianna University School of Medicine, 216-8511 - Kawasaki city/JP
  • 6 Department Of Frontier Science For Cancer And Chemotherapy, Osaka University Graduate School of Medicine, 565-0871 - Suita/JP
  • 7 Department Of Gastrointestinal Medical Oncology, Shikoku Cancer Center, 791-0280 - Matsuyama/JP
  • 8 Department Of Gastrointestinal And Medical Oncology, National Kyushu Cancer Center, Fukuoka/JP
  • 9 Clinical research Support Office, National Cancer Center Hospital East, Kashiwa/JP
  • 10 Clinical research Support Office, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 11 Pathology Division, Research Center For Innovative Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 12 Division Of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya/JP
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Resources

Abstract 1986

Background

While BRAF mutations occur in 10-15% of metastatic colorectal cancer (mCRC), BRAF Non-V600E mutations was recently reported with ranging 2.2 - 5.2%. We have reported that BRAF Non-V600E could be a negative impact on survival outcome as well as anti-EGFR antibody treatment for pretreated mCRC patients (Shinozaki E, et al. Br J Cancer 2017). In addition, simultaneous inhibitions of MEK, BRAF and EGFR exhibited most potent anti-tumor activities in BRAF Non-V600E mutant cell lines and xenografted models (unpublished data).

Trial design

BIG BANG study is a multicenter phase II study to assess efficacy, safety and proof-of-concept of the triple combinations of binimetinib (BINI) + encorafenib (ENCO) + cetuximab (CETUX) in patients with BRAF Non-V600E mutated mCRC, identified by either tumor tissue-based analysis (primary analysis cohort) or circulating tumor DNA (ctDNA) analysis (liquid biopsy cohort). Key eligibility criteria includes ECOG PS ≤ 1; mCRC with BRAF Non-V600E mutant and RAS wild-type; refractory or intolerant to at least one fluoropyrimidine-based regimen (including irinotecan or oxaliplatin) and no prior history of anti-EGFR antibody and regorafenib. Enrolled patients receive BINI (45 mg, BID), ENCO (300 mg, QD), and CETUX (initially 400 mg/m2, and subsequently 250 mg/m2, QW), which are same recommended doses as the BEACON CRC trial (NCT02928224). In addition, the natural history data of patients with BRAF Non-V600E mutations who do not meet the eligibility criteria are collected as a historical control. The primary endpoint is the objective response rate (ORR) for primary analysis cohort. A sample size of the primary analysis cohort is calculated to be 21 on the hypothesis that the threshold ORR is 6% and expected ORR is 30%, with a significant level of 2.5% (one-sided) and power of 80%. Furthermore, paired tissue and blood samples will be obtained for pharmacodynamics analysis before study treatment, pre-dose of second cycle, and after disease progression. To our best knowledge, this is the first study targeting BRAF Non-V600E mutated mCRC.

Clinical trial identification

UMIN000031857 and 000031860.

Legal entity responsible for the study

Hideaki Bando.

Funding

The Japan Agency for Medical Research and Development.

Editorial Acknowledgement

Disclosure

H. Bando: Research funding: AstraZeneca, Sysmex, Falco biosystemes. T.E. Nakajima: Personal financial interests: Eli Lilly, Sanofi, Chugai, Sawai, Bayer, Bristol, Taiho, Merck, Ono, Takeda, Mochida, MSD; Institutional financial interests: Ono, Taiho, A2 Health Care, JCRO, Daiichi-Sankyo, Mediscience Planning. T. Nishina: Grants, honoraria: Ono, Merck Serono, Yakult, Taiho, Chugai. T. Esaki: Grant: Taiho, Eli Lilly, Eisai, Daiichi-Sankyo, DS Pharma, Merck Serono, Ono, Nihon Kayaku, Novartis, AstraZeneca, Boehringer, MSD, Astellas, Bayer, Pfizer, Yakult; Personal fees: Taiho, Bristol, Eli Lilly, Eisai, Daiichi-Sankyo, Merck Serono, Chugai, Ono, Takeda, Kyowa-Kirin, Nihon Kayaku. S. Nomura: Honoraria: Taiho. T. Yoshino: Grant: MSD, Sanofi, Sumitomo Dainippon Pharma, Chugai, GlaxoSmithKline, Nippon Boehringer Ingelheim; Personal fees: Sanofi, Chugai, Eli Lilly, Merck Serono. All other authors have declared no conflicts of interest.

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