Vol 4 No 1 (2018): Current Issue
Research Article

BIW-8962, an Anti GM2 Ganglioside Monoclonal Antibody, in Previously Treated Advanced/Recurrent Lung Cancer: a Phase I/II Study: None

Park K
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul, Republic of Korea
Lee JS
Department of Hematology-Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Kim SW
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
Lee DH
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
Kang JH
Division of Medical Oncology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of Korea
Cho BC
Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
Kim JH
Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
Shiraishi N
Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
Strout V
Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ, USA
Published November 20, 2018

Abstract

BIW-8962 is a monoclonal antibody to GM2 ganglioside that shows pre-clinical activity towards lung cancer cell lines and in an animal model bearing small-cell lung cancer (SCLC) xenografts. In phase I, patients (N=16) with advanced, recurrent lung cancer received BIW-8962 (1-10 mg/kg) intravenously every 3 weeks. There were no dose-limiting toxicities and the maximum tolerated dose was not established. The highest dose (10 mg/kg) was administered to patients with advanced, recurrent SCLC (N=21) in phase II. The phase II study was prematurely terminated due to lack of efficacy. Objective response rate was 5% (95% CI: 0.1-24.9%) in the efficacy evaluable population (N=20). One patient showed a durable partial response and there were a few with stable disease, which was generally not durable. No pattern of consistent toxicity was observed across the phases: there were no treatment-related adverse events (AEs) grade ? 3, serious AEs, AEs leading to discontinuation of BIW-8962, or deaths. Exploratory analysis of circulating tumor cells and other potentially predictive orpharmacodynamic markers did not reveal any results consistent with an effect from BIW-8962. Given the complete lack of response in the study population, further development of BIW- 8962 has been discontinued. The reason for the lack of clinical activity with BIW-8962 is unknown. It is hoped that the negative findings of this study will contribute to other investigations of GM2 as a therapeutic target, possibly by combination therapy, and of alternative tumor markers in patients with SCLC.