Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study

Talquetamab, a G protein-coupled receptor class C group 5 member D-targeting bispecific antibody for relapsed/refractory multiple myeloma (R/R MM), plus daratumumab, may lead to deeper and more durable responses than either therapy alone. In the phase 1b TRIMM-2 study, patients with R/R MM (at least 3 previous lines of therapy or double refractory to a proteasome inhibitor and an immunomodulatory drug) received subcutaneous talquetamab 0.4 mg/kg weekly (QW; "QW cohort") or 0.8 mg/kg every other week (Q2W cohort) plus daratumumab 1800 mg per the approved schedule. The primary end point was safety. Secondary end points included overall response and duration of response. Progression-free survival was an exploratory end point. Sixty-five patients (median 5 previous lines of therapy; 61.5% triple-class refractory; 24.6% bispecific antibody exposed) received talquetamab plus daratumumab (QW, n = 14; Q2W, n = 51; median follow-up of 18.6 months). Most common adverse events were oral events, skin events, cytokine release syndrome, and infections. Grade 3 or 4 events occurred in 81.5%. Two patients had dose-limiting toxicities, both in the Q2W cohort (grade 3 stomatitis/oral mucositis, and grade 3 maculopapular rash). Responses occurred in 71.4% (QW cohort) and 82.4% (Q2W cohort) of patients. Median progression-free survival was 23.3 and 21.2 months, respectively, in each cohort. Pharmacodynamic results suggest the immunomodulatory action of daratumumab contributes to a conducive environment for talquetamab by reducing immunosuppressive cells. Talquetamab plus daratumumab demonstrated promising efficacy outcomes in patients with heavily pretreated disease, with a safety profile consistent with each agent as monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT04108195.

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Publication Details

Journal
Blood
Published
2025-09-22
DOI
https://doi.org/10.1182/blood.2025029360
Citations
8
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
14.16

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article

Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study

Sheri Skerget, Ajai Chari, Laura Rosiñol, Katja Christina Weisel et al.
8 citations
Blood
Multiple Myeloma Research and Treatments
14.16
article

Talquetamab plus daratumumab for the treatment of relapsed or refractory multiple myeloma in the TRIMM-2 study

Sheri Skerget, Ajai Chari, Laura Rosiñol, Katja Christina Weisel, Kalpana Bakshi, María‐Victoria Mateos, Niels W.C.J. van de Donk, Anita D’Souza, Jaszianne Tolbert, Donna Reece, Manisha Bhutani, Albert Oriol, Hartmut Goldschmidt, Bhagirathbhai Dholaria, Raluca Verona, Thomas G. Martin, Nizar Jacques Bahlis, Thomas J. Prior, Daniel Morillo, Deeksha Vishwamitra, Lijuan Kang, Paula Rodríguez‐Otero, Ralph Wäsch, Lien Vandenberk, Sangmin Lee, Damiette Smit
article en
8 citations

Abstract

Talquetamab, a G protein-coupled receptor class C group 5 member D-targeting bispecific antibody for relapsed/refractory multiple myeloma (R/R MM), plus daratumumab, may lead to deeper and more durable responses than either therapy alone. In the phase 1b TRIMM-2 study, patients with R/R MM (at least 3 previous lines of therapy or double refractory to a proteasome inhibitor and an immunomodulatory drug) received subcutaneous talquetamab 0.4 mg/kg weekly (QW; "QW cohort") or 0.8 mg/kg every other week (Q2W cohort) plus daratumumab 1800 mg per the approved schedule. The primary end point was safety. Secondary end points included overall response and duration of response. Progression-free survival was an exploratory end point. Sixty-five patients (median 5 previous lines of therapy; 61.5% triple-class refractory; 24.6% bispecific antibody exposed) received talquetamab plus daratumumab (QW, n = 14; Q2W, n = 51; median follow-up of 18.6 months). Most common adverse events were oral events, skin events, cytokine release syndrome, and infections. Grade 3 or 4 events occurred in 81.5%. Two patients had dose-limiting toxicities, both in the Q2W cohort (grade 3 stomatitis/oral mucositis, and grade 3 maculopapular rash). Responses occurred in 71.4% (QW cohort) and 82.4% (Q2W cohort) of patients. Median progression-free survival was 23.3 and 21.2 months, respectively, in each cohort. Pharmacodynamic results suggest the immunomodulatory action of daratumumab contributes to a conducive environment for talquetamab by reducing immunosuppressive cells. Talquetamab plus daratumumab demonstrated promising efficacy outcomes in patients with heavily pretreated disease, with a safety profile consistent with each agent as monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT04108195.

BloodVol. 146(24)
Johnson & Johnson (United States) (US), City College of San Francisco (US), Universität Hamburg (DE), University of Freiburg (DE), University of Calgary (CA), University of California, San Francisco (US), Universidad de Salamanca (ES), Medical College of Wisconsin (US), Heidelberg University (DE), University Medical Center Freiburg (DE), University Hospital Heidelberg (DE), Princess Margaret Cancer Centre (CA), Nivalis Therapeutics (United States) (US), Levine Cancer Institute (US), Springhouse (US), Institut Català d'Oncologia (ES), Amsterdam Neuroscience (NL), University Medical Center Hamburg-Eppendorf (DE), Hospital Clínic de Barcelona (ES), Province of Antwerp (BE), Alberta Bone and Joint Health Institute (CA), Hospital Universitario Fundación Jiménez Díaz (ES), Instituto de Investigación Biomédica de Salamanca (ES), Clinica Universidad de Navarra (ES), Johnson & Johnson (Israel) (IL), Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES), Centro de Investigación del Cáncer (ES), Amsterdam University Medical Centers (NL), Johnson & Johnson (Netherlands) (NL), Centro de Investigación Biomédica en Red de Cáncer (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Vrije Universiteit Amsterdam (NL), University of Amsterdam (NL), Vanderbilt University Medical Center (US)
Amgen, Pfizer, Sanofi, Gilead Sciences, Celgene, Regeneron Pharmaceuticals, Prothena, Adaptive Biotechnologies, Servier, Genentech, Onyx Pharmaceuticals, Chugai Pharmaceutical, Kite Pharma
Openalex Percentile: Top 1%
Multiple Myeloma Research and Treatments
14.16
DOIOpen Access PDFOpenAlex
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