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Clinical Trial
. 2025 Sep;122(3):421-433.
doi: 10.1007/s12185-025-03991-5. Epub 2025 May 9.

Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed/refractory MM

Shinsuke Iida  1 , Kazutaka Sunami  2 , Shigeki Ito  3 , Junichiro Yuda  4 , Ei Fujikawa  5 , Mikihiro Takamoto  5 , Kensuke Aida  5 , Hiroshi Yamazaki  5 , Marimo Takahashi  6 , Tadao Ishida  7
Affiliations
Clinical Trial

Phase 1 study of talquetamab, a humanized GPRC5D x CD3 bispecific antibody, in Japanese patients with relapsed/refractory MM

Shinsuke Iida et al. Int J Hematol. 2025 Sep.

Abstract

The bispecific antibody talquetamab demonstrated substantial responses in heavily pretreated relapsed or refractory multiple myeloma (RRMM) in the global phase 1/2 MonumenTAL-1 study. This study, evaluated the safety and efficacy of talquetamab in Japanese patients with RRMM pretreated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. The primary endpoints were frequency and type of treatment-emergent adverse events (TEAEs) and serious AEs including dose-limiting toxicity (DLT). The secondary endpoints were overall response (ORR; partial response or better), duration of, and time to response. At data cutoff, 15 patients had received subcutaneous talquetamab at three doses (Cohort 1: 135 µg/kg weekly [QW, n = 4]; Cohort 2: 400 µg/kg [QW, n = 5]; Cohort 3: 800 µg/kg [Q2W, n = 6]). No DLTs, deaths, or AE-related dose reductions/treatment discontinuation were observed. Common TEAEs were neutropenia (60.0%), lymphopenia (53.3%), and CRS (46.7%). TEAEs of clinical interest (all Grade ≤ 2) were dysgeusia, skin toxicity, nail disorder, and dry mouth. With an overall median follow-up of 9.0 months, the ORR was 60.0% (95% confidence interval 32.3%, 83.7%). Talquetamab showed substantial responses in Japanese patients with RRMM, consistent with the global MonumenTAL-1 study, supporting its potential as a new standard of care for Japanese RRMM patients.

Keywords: Immunotherapy; Japanese population; Relapsed/refractory multiple myeloma; Talquetamab.

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Conflict of interest statement

Declarations. Conflict of interest: 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 and paid to the institution. Consulting fees received from Abbvie, Astrazeneca, BMS, GSK, Janssen, Novartis, Otsuka, Pfizer, and Sanofi. Payment or honoraria received from Astrazeneca, BMS, Janssen, Pfizer, Sanofi, and Takeda, paid to the author. Other financial or non-financial interests received from Chugai as subsidy. Kazutaka Sunami: Grants as 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. Shigeki Ito: Grant or research funding received from Abbvie, BMS, GSK, Janssen, Pfizer, and Sanofi. Honoraria received from BMS, Janssen, Pfizer, Takeda and Sanofi. Junichiro Yuda: has received research funding from AbbVie, Amgen, BMS, Chugai, Daiichi Sankyo, Genmab, Incyte, Janssen, Novartis, Mitsubishi Tanabe, MSD, Sumitomo, and Takeda. Participated on a data safety monitoring board or advisory board for Janssen. Ei Fujikawa: Employee of Janssen Pharmaceutical K.K. Mikihiro Takamoto: Employee of Janssen Pharmaceutical K.K. 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. Marimo Takahashi: Employee of Janssen Pharmaceutical K.K. Owns stock or stock options in J&J innovative medicine. Tadao Ishida: Grants as Research funding received from Alexion pharma, BMS, GSK, Janssen, Pfizer, Prothena, Sanofi, and Takeda. Payment or honoraria received from BMS, CSL Behring, Janssen, Ono, Pfizer, Sanofi, and Takeda. Ethical approval: The study was conducted in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonization guidelines for Good Clinical Practice. The study, protocol along with any amendments, was approved by the institutional review boards at each participating study site. All patients also provided written informed consent.

Figures

Fig. 1
Fig. 1
Patient disposition. All patients in Cohort 1 and 2 patients in Cohort 2: After disease progression as per the IMWG criteria, the patients received ethical supply, but the administration was discontinued due to further disease progression. One patient each in Cohort 2 and 3: Withdrawal by patient
Fig. 2
Fig. 2
Linear mean (SD) pre-dose serum concentration–time profiles of talquetamab after SC administration of talquetamab. Treatments at 135 µg/kg weekly (with step-up doses of 10 and 45 µg/kg), at 400 µg/kg weekly (with step-up doses of 10 and 60 µg/kg), and at 800 µg/kg biweekly (with step-up doses of 10, 60 and 300 µg/kg)
Fig. 3
Fig. 3
Response to talquetamab therapy in patients with RRMM. Treatments: at Cohort 1, 135 µg/kg Weekly (with step-up doses of 10 and 45 µg/kg), at cohort 2, 400 µg/kg weekly (with step-up doses of 10 and 60 µg/kg), and at cohort 3, 800 mg/kg biweekly (with step-up doses of 10, 60 and 300 µg/kg). Response was assessed by investigator, based on International Myeloma Working Group (IMWG) consensus criteria (2016)
Fig. 4
Fig. 4
Responses over time in patients who received talquetamab. Treatments: at cohort 1, 135 µg/kg weekly (with step-up doses of 10 and 45 µg/kg), at cohort 2, 400 µg/kg weekly (with step-up doses of 10 and 60 µg/kg), and at cohort 3, 800 mg/kg biweekly (with step-up doses of 10, 60 and 300 µg/kg). Response was assessed by investigator, based on International Myeloma Working Group (IMWG) consensus criteria (2016). AE adverse events, CR complete response, D/C discontinued, PD progressive disease, PR partial response, sCR stringent complete response, VGPR very good partial response
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