Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L)

Yuichi Ozawa; Yasuhiro Koh; Tetsunari Hase; Kenji Chibana; Kyoichi Kaira; Kyoichi Okishio; Eiki Ichihara; Shuji Murakami; Mototsugu Shimokawa; Nobuyuki Yamamoto

doi:10.1177/17588359231225046

Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L)

Ther Adv Med Oncol. 2024 Jan 27:16:17588359231225046. doi: 10.1177/17588359231225046. eCollection 2024.

Authors

Yuichi Ozawa^{1

2}, Yasuhiro Koh^{3

4}, Tetsunari Hase⁵, Kenji Chibana⁶, Kyoichi Kaira⁷, Kyoichi Okishio⁸, Eiki Ichihara⁹, Shuji Murakami¹⁰, Mototsugu Shimokawa¹¹, Nobuyuki Yamamoto³

Affiliations

¹ Department of Respiratory Medicine, Hamamatsu Medical Center, 328 Tomitsuka-cho, Naka-ku, Hamamatsu, Shizuoka 432-8580, Japan.
² Internal Medicine III, Wakayama Medical University, Wakayama City, Wakayama 641-0012, Japan.
³ Internal Medicine III, Wakayama Medical University, Wakayama City, Wakayama, Japan.
⁴ Center for Biomedical Sciences, Wakayama Medical University, Wakayama City, Wakayama, Japan.
⁵ Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
⁶ Department of Respiratory Medicine, National Hospital Organization Okinawa National Hospital, Ginowan, Okinawa, Japan.
⁷ Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
⁸ Department of Internal Medicine, National Hospital Organization Kinki-chuo Chest Medical Center, Sakai City, Osaka, Japan.
⁹ Center for Clinical Oncology, Okayama University Hospital, Okayama, Okayama, Japan.
¹⁰ Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
¹¹ Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.

Abstract

Background: ALK-tyrosine kinase inhibitors (ALK-TKIs) are effective for treating non-small-cell lung cancer with ALK gene rearrangement; however, resistance is inevitable. Brigatinib is a unique ALK-TKI that is effective against many resistance mutations. However, data on factors associated with its efficacy and resistance mechanisms are limited.

Objectives: This study will evaluate the efficacy and safety of brigatinib in the real world and explore factors related to its efficacy, safety, and resistance mechanisms.

Design: Prospective observational study.

Ethics: This study is approved by the Ethics Committee of Wakayama Medical University. Written informed consent will be obtained from all patients before study-related procedures.

Methods and analysis: This study comprises three cohorts. Cohorts A, B, and 0 will enroll patients receiving alectinib as the first ALK-TKI, receiving alectinib as the first ALK-TKI and subsequently cytotoxic agents and/or lorlatinib after alectinib, and without a history of ALK-TKI, respectively. Overall, 100, 30, and 50 patients will be enrolled in Cohorts A, B, and 0, respectively. Circulating tumor DNA before starting brigatinib and at disease progression will be analyzed in all cohorts using a hypersensitive next-generation sequencing (NGS) PGDx Elio plasma resolve panel. Serum protein levels will be analyzed using the Milliplex xMAP assay system with a Luminex 200 (Luminex, Austin, USA). The enrollment period is 31 months and the patients will be observed for 2 years after enrollment. Archived tissues will be collected for NGS analysis, gene expression analysis, and immunohistochemistry staining 1 year after completion of registration. Quality of life and safety evaluation using electronic patient-reported outcomes will be investigated.

Discussion: This study will elucidate predictors of ALK-TKI efficacy and resistance mechanisms and evaluate the efficacy and safety of brigatinib in a real-world setting. The results will provide crucial information for establishing treatment strategies, discovering novel biomarkers, and developing new therapeutic agents.

Trial registration: UMIN000042439.

Keywords: ALK inhibitors; alectinib; brigatinib; non-small-cell lung cancer; observational study.