Clinical Trial Protocol

The BEETS (JACCRO CC-18) trial: an observational and translational study of BRAF-mutated metastatic colorectal cancer

Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osakasayama, Osaka 589-8511, Japan

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Ryo Matoba

DNA Chip Research Inc., 1-15-1, Kaigan, Minato-ku, Tokyo 105-0022, Japan

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Satoshi Yuki

https://orcid.org/0000-0002-2039-3062

Department of Gastroenterology & Hepatology, Hokkaido University Hospital, Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido 060-8648, Japan

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Manabu Shiozawa

Department of Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi Ward, Yokohama, Kanagawa 241-8515, Japan

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Akihito Tsuji

Department of Clinical Oncology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan

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Eisuke Inoue

https://orcid.org/0000-0002-1652-7769

Showa University Research Administration Center, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

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Kei Muro

https://orcid.org/0000-0002-5572-743X

Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan

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Wataru Ichikawa

https://orcid.org/0000-0001-5543-4488

Division of Medical Oncology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa 227-8501, Japan

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Masashi Fujii

https://orcid.org/0000-0001-6707-6040

Japan Clinical Cancer Research Organization (JACCRO), 1-64 Kanda-Jimbocho, Chiyoda-ku, Tokyo 101-0051, Japan

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Yu Sunakawa

*Author for correspondence: Tel.: +81 449 778 111;

E-mail Address: y.suna0825@gmail.com

https://orcid.org/0000-0002-0163-7543

Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan

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Published Online:13 Jun 2023https://doi.org/10.2217/fon-2023-0209

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Abstract

For BRAF V600E-mutated metastatic colorectal cancer (mCRC), the BEACON phase 3 trial showed survival benefit of triplet therapy with cetuximab (anti-EGFR antibody), encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) as well as doublet therapy with cetuximab and encorafenib over irinotecan-based chemotherapy plus anti-EGFR antibody. Both regimens are standards of care in Japan, but definite biomarkers for predicting efficacy and selecting treatment remain lacking. The mechanisms underlying resistance to these regimens also warrant urgent exploration to further evolve treatment. This prospective observational/translational study evaluated real-word clinical outcomes with cetuximab and encorafenib with or without binimetinib for BRAF-mutated mCRC patients and investigated biomarkers for response and resistance by collecting blood samples before and after treatment.

Clinical Trial Registration:UMIN000045530 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051983)

Plain language summary - The BEETS (JACCRO CC-18) trial: a study that observes the effect of targeted therapies for patients with advanced colorectal cancer that has BRAF mutation

The BEETS trial is a study that looks at how well two combinations of targeted therapies (cetuximab + encorafenib with or without binimetinib) work and how safe they are for patients with advanced colorectal cancer that has a mutation (change) in the BRAF gene. In this trial, patients participate voluntarily instead of being assigned to one of the two therapy groups. When a patient has BRAF-mutated advanced colorectal cancer, it means that the cancer cells in their body have changes in a gene called BRAF. This gene normally produces a protein called BRAF, which is involved in the growth of cells. However, when there is a mutation in this gene, it can cause the production of an overactive BRAF protein, leading to fast and excessive cell growth and division. For patients with BRAF-mutated advanced colorectal cancer, combinations of targeted therapies have been found to be effective as a second- or third-line treatment, based on the results of a phase 3 clinical trial. The main goal of the BEETS trial is to evaluate how well these treatments work and how safe they are when used in real-world clinical practice. Additionally, the study will use laboratory tests (liquid biopsy) to explore new biomarkers that can help predict how well a treatment will work and assist in selecting the most suitable treatment plans. We hope that the findings of this study will contribute to improving the overall management of this specific type of cancer.

Tweetable abstract

The protocol paper of the BEETS (JACCRO CC-18) trial, a prospective observational/translational study of BEACON regimens for BRAF-mutated mCRC, is now available in Future Oncology.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 19, No. 17

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History

Received 15 March 2023

Accepted 26 May 2023

Published online 13 June 2023

Published in print June 2023

Information

Keywords

Acknowledgments

The authors acknowledge the patients participating in this study and their families, as well as staff at the investigational sites.

Financial & competing interests disclosure

This study is funded by Ono Pharmaceutical Co., Ltd. C Inagaki has received honoraria as lecture fees from MSD and Taiho Pharmaceutical, and has received research funding from Eisai and Astellas Pharma. Y Sunakawa has received honoraria from Takeda Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, and Merck Biopharma, along with grants from IQVIA, Ono Pharmaceutical, CMIC ShiftZero, PRA Health Sciences, Amgen, and Parexel, and contributions or an endowed chair from Takeda Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Sanofi, and EN Otsuka Pharma. R Matoba is a founder and Chief Executive Officer of DNA Chip Research. S Yuki has received honoraria from Chugai Pharmaceutical, Eli Lilly Japan, Takeda Pharmaceutical, Bayer Yakuhin, Bristol-Myers Squibb, Taiho Pharmaceutical, MSD, Ono Pharmaceutical, Merck Biopharma, Nippon Boehringer Ingelheim, and Daiichi Sankyo. M Shiozawa has nothing to disclose. A Tsuji has received lecture fees from Merck Biopharma, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, and Daiichi Sankyo. E Inoue has received lecture fees from Bristol-Myers Squibb and Eisai. K Muro has received research funding from Sanofi, Eisai, Astellas, Amgen, Daiichi Sankyo, Novartis, Taiho, MSD, Ono, and Chugai, and has received honoraria as lecture fees from Eli Lilly Japan, Daiichi Sankyo, Ono, Taiho, and Bristol-Myers Squibb. W Ichikawa has received research funding from Chugai Pharma, Taiho Pharma, Shionogi & Co., Eli Lilly Japan, and Daiichi Sankyo Co., and has received lecture fees from Chugai Pharma, Takeda Pharma, Merck Biopharma, Bayer Yakuhin, Taiho Pharma, Yakult Honsha, Bristol-Myers Squibb, AstraZeneca, Kowa Kirin, and Nippon Kayaku. Masashi Fujii has nothing to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the ethics committee at St. Marianna University (approval No. 5413) and was developed in accordance with the Declaration of Helsinki. Written informed consent must be obtained from all patients who are enrolled in this study.

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