A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients.
Competing Interests: Declaration. Conflict of interest: Tadao Ishida: Research funding received from Alexion pharma, BMS, GSK, Janssen, Pfizer, Prothena, Sanofi, and Takeda. Honoraria received from BMS, CSL Behring, Janssen, Ono, Pfizer, Sanofi, and Takeda. Yoshiaki Kuroda: Payment or honoraria received from Amgen, Asahi Kasei Pharma, Astrazeneca, BMS, Janssen, Ono, Sanofi, SymBio Pharmaceuticals, and Takeda Pharmaceuticals. Kosei Matsue: Grants or contract received from Astrazeneca. Takuya Komeno: Grants or contracts received from Abbvie, BMS, Janssen Pharmaceutical K.K., and Sanofi. Takuro Ishiguro: Payment or honoraria received from Janssen Pharmaceutical K.K., Sanofi, BMS, Ono Pharmaceutical, Takeda Pharmaceutical Company Limited, and Novartis. Jun Ishikawa: None. Toshiro Ito: None. Hiroshi Kosugi: Payment or honoraria received from Abbvie G.K., Asahi Kasei Pharma, Astrazeneca K.K., Beckton Dickinson K.K., BMS K.K., Chugai, GSK K.K., Janssen Pharmaceutical K.K., Japan Blood Products Organization, Kyowa Kirin, Kissei Pharmaceutical, Nippon Shinyaku, Novartis Pharma K.K., Novo Nordisk Pharma Japan, Ono, Sanofi K.K., and Takeda. Kazutaka Sunami: Research funding received from: Abbvie, Beigene, BMS, Chugai, GSK, Incyte, Janssen, Kyowa Kirin, Mitsubishi Tanabe, Novartis, Ono, Otsuka, Pfizer, and Sanofi. Honoraria received from BMS, Janssen, and Sanofi. Kazuko Nishikawa: Employee of Janssen Pharmaceutical K.K. Kazuhiro Shibayama: Employee of Janssen Pharmaceutical K.K., and own stock or stock options in Johnson & Johnson. Kensuke Aida: Employee of Janssen Pharmaceutical K.K. Hiroshi Yamazaki: Employee of Janssen Pharmaceutical K.K., own stocks or stock options in Kameya Shoji Co., Ltd. Mitsuo Inagaki: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson & Johnson. Hisanori Kobayashi: Employee of Janssen Pharmaceutical K.K., and own stocks or stock options in Johnson and Johnson. Shinsuke Iida: All support for the present manuscript received from Janssen. Grants received from Abbvie, Amgen, BMS, Daiichi Sankyo, GSK, Janssen, Novartis, Ono, Otsuka, Pfizer Sanofi, Shionogi, and Takeda. Consulting fees received from Abbvie, Astrazeneca, BMS, GSK, Janssen, Novartis, Otsuka, Pfizer, and Sanofi. Payment or honoraria received from Astrazeneca, BMS, Janssen, Ono, Pfizer, Sanofi, and Takeda. Other financial or non-financial interests received from Chugai. Ethical approval: The study protocol and associated study documents were approved by the Institutional Review Board. Good Clinical Practice (GCP) guidelines, established by the International Council for Harmonization (ICH), and all relevant regulatory requirements were followed during the conduct of this study.
(© 2024. The Author(s).)