Updated Results of Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma with Prior Exposure to T-Cell Redirecting Therapies: Results of the Phase 1/2 MonumenTAL-1 Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.3377-3377
• Main Authors: Jakubowiak, Andrzej J, Anguille, Sebastien, Karlin, Lionel, Chari, Ajai, Schinke, Carolina, Rasche, Leo, San-Miguel, Jesus, Campagna, Michela, Hilder, Brandi W, Masterson, Tara J, Qin, Xiang, Renaud, Thomas, Tolbert, Jaszianne, Vishwamitra, Deeksha, Skerget, Sheri, Moreau, Philippe
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-187242

Introduction: Novel T-cell redirecting therapies (TCR), including chimeric antigen receptor T-cell therapy (CAR-T) and bispecific antibodies (BsAbs), are important new treatment options for patients (pts) with relapsed/refractory multiple myeloma (RRMM) but result in a new unmet need for pts who relapse following these therapies. Talquetamab is the most advanced BsAb therapy targeting G protein-coupled receptor family C group 5 member D (GPRC5D), a novel antigen that is overexpressed on malignant plasma cells but is expressed at low levels on B cells and bone marrow progenitors. Previous results from the phase 1/2 MonumenTAL-1 study (NCT03399799/NCT04634552) demonstrated deep and durable responses with talquetamab in pts with RRMM, with an overall response rate (ORR) of >71% in 288 pts naive to TCR and 65% in 51 pts with prior TCR. Here, we present updated results in pts with prior TCR, including an additional 19 pts enrolled since the prior analysis. Methods: Eligible pts for phase 1 of the study had progressed on or could not tolerate established multiple myeloma therapies.In phase 2, eligible pts had been exposed to ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. The current analysis includes all pts across phase 1 and 2 of the study who received 1 of the 2 recommended phase 2 doses of subcutaneous talquetamab (0.4 mg/kg weekly [QW] or 0.8 mg/kg every other week [Q2W]) and who were exposed to a TCR (prior CAR-T and BsAb), as well as pts exposed to both a TCR and a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate (ADC). Results: As of Jan 17, 2023, 70 pts were enrolled with prior TCR. Overall, 44 (63%) were