Forimtamig, a GPRC5DxCD3 bispecific antibody with a novel 2:1 format, in relapsed/refractory multiple myeloma

We report the results from a Phase 1 study (NCT04557150) evaluating subcutaneous (SC) forimtamig, a novel GPRC5DxCD3 bispecific antibody with a 2:1 configuration, in relapsed/refractory multiple myeloma (RRMM). After dose-escalation, backfilling at optimized target doses in combination with weekly (step-up: Cycle [C] 1 Day [D] 1 and C1D8; target: C1D15) and condensed (step-up: C1D1 and C1D4; target: C1D8) step-up dosing was pursued for benefit-risk assessment. Primary objectives were evaluating safety/tolerability and determining the maximum tolerated dose (MTD) and recommended Phase 2 dose/schedule. Secondary objectives included pharmacokinetics, immunogenicity and anti-tumor activity. In total, 171 patients were enrolled (median age: 64.0 years; high-risk cytogenetics: 32.2%; triple-class refractory: 60.2%). The starting C1D1 dose was 0.05 mg. Dose-limiting toxicities occurred in 20 patients (11.7%). MTD was not identified. Dose-escalation concluded at 7.2 mg target dose due to accumulating toxicity. The most common adverse event (AE) was cytokine release syndrome (75.4%). Grade 5 AEs occurred in 11 patients (6.4%); two events were considered treatment-related. Across all cohorts, the overall response rate (ORR) was 59.6%. At the optimized target doses (0.75 mg/1.5 mg), ORR was 71.7% with the condensed schedule (n = 46) and 47.1% with the weekly schedule (n = 34). Early soluble B-cell maturation antigen reduction and minimal residual disease negativity were associated with improved progression-free survival. SC forimtamig demonstrated potent and durable activity in RRMM, which could be enhanced with a condensed step-up schedule. On-target, off-tumor toxicities were common, highlighting the narrow therapeutic window for GPRC5D as a target for T-cell-engaging bispecific antibodies.

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Journal
Blood Advances
Published
2026-09-30
DOI
https://doi.org/10.1182/bloodadvances.2026020498
Primary Topic
Monoclonal and Polyclonal Antibodies Research
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article
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article

Forimtamig, a GPRC5DxCD3 bispecific antibody with a novel 2:1 format, in relapsed/refractory multiple myeloma

Christopher Parrish, Enrique M. Ocio, Iryna Dekhtiarenko, Nassim Sleiman et al.
Blood Advances
Monoclonal and Polyclonal Antibodies Research
article

Forimtamig, a GPRC5DxCD3 bispecific antibody with a novel 2:1 format, in relapsed/refractory multiple myeloma

Christopher Parrish, Enrique M. Ocio, Iryna Dekhtiarenko, Nassim Sleiman, Wolfgang Jacob, Hans‐Joachim Helms, María‐Victoria Mateos, Emilie Schindler, Salomon Manier, Carmelo Carlo‐Stella, Rodger Edwin Tiedemann, Paolo Corradini, Ida Bruun Kristensen, Elena Zamagni, Orwa Albitar, Cyrille Touzeau, Ann-Marie E Bröske, Francesco Volzone, Vu Long Tran, Paula Rodríguez‐Otero, Georgina Meneses‐Lorente, Rakesh Popat, Cyrille Hulin, Simon James Harrison, Sung‐Soo Yoon, Fritz Offner, Martin Weisser, Anna Caroline Hasselbalch, Chang-Ki Min, Eva Rossmann, Natalie Dimier, Kihyun Kim
article en

Abstract

We report the results from a Phase 1 study (NCT04557150) evaluating subcutaneous (SC) forimtamig, a novel GPRC5DxCD3 bispecific antibody with a 2:1 configuration, in relapsed/refractory multiple myeloma (RRMM). After dose-escalation, backfilling at optimized target doses in combination with weekly (step-up: Cycle [C] 1 Day [D] 1 and C1D8; target: C1D15) and condensed (step-up: C1D1 and C1D4; target: C1D8) step-up dosing was pursued for benefit-risk assessment. Primary objectives were evaluating safety/tolerability and determining the maximum tolerated dose (MTD) and recommended Phase 2 dose/schedule. Secondary objectives included pharmacokinetics, immunogenicity and anti-tumor activity. In total, 171 patients were enrolled (median age: 64.0 years; high-risk cytogenetics: 32.2%; triple-class refractory: 60.2%). The starting C1D1 dose was 0.05 mg. Dose-limiting toxicities occurred in 20 patients (11.7%). MTD was not identified. Dose-escalation concluded at 7.2 mg target dose due to accumulating toxicity. The most common adverse event (AE) was cytokine release syndrome (75.4%). Grade 5 AEs occurred in 11 patients (6.4%); two events were considered treatment-related. Across all cohorts, the overall response rate (ORR) was 59.6%. At the optimized target doses (0.75 mg/1.5 mg), ORR was 71.7% with the condensed schedule (n = 46) and 47.1% with the weekly schedule (n = 34). Early soluble B-cell maturation antigen reduction and minimal residual disease negativity were associated with improved progression-free survival. SC forimtamig demonstrated potent and durable activity in RRMM, which could be enhanced with a condensed step-up schedule. On-target, off-tumor toxicities were common, highlighting the narrow therapeutic window for GPRC5D as a target for T-cell-engaging bispecific antibodies.

Blood Advances
Roche (Switzerland) (CH), Universidad de Cantabria (ES), Humanitas University (IT), University College London Hospitals NHS Foundation Trust (GB), Seoul National University (KR), University of Southern Denmark (DK), Leeds Teaching Hospitals NHS Trust (GB), Peter MacCallum Cancer Centre (AU), Ghent University Hospital (BE), Auckland City Hospital (NZ), Samsung Medical Center (KR), Rigshospitalet (DK), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), St. Mary's Hospital (US), Roche (United Kingdom) (GB), Instituto de Investigación Marqués de Valdecilla (ES), St Mary's Hospital (GB), Instituto de Investigación Biomédica de Salamanca (ES), Clinica Universidad de Navarra (ES), UCL Biomedical Research Centre (GB), Centro de Investigación del Cáncer (ES), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), The Catholic University of Korea Seoul St. Mary's Hospital (KR), IRCCS Humanitas Research Hospital (IT), Sungkyunkwan University (KR), Nantes Université (FR)
Openalex Percentile: Top 12%
Monoclonal and Polyclonal Antibodies Research
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