Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1

Background

• Talquetamab is a novel first-in-class, off-the-shelf, T cell–redirecting bispecific antibody directed against the new antigen target GPRC5D.
• GPRC5D is a novel antigen target in myeloma that is highly expressed on malignant plasma cells and that has limited expression in normal human tissues, including hematopoietic stem cells.
• Talquetamab therapy produced an overall response rate (ORR) of 64% to 70% with use of 0.406 mg/kg given subcutaneously (SC) once weekly and 0.8 mg/kg SC given every other week in the phase 1 MonumenTAL-1 study (NCT03399799).

Methods

• Key objectives
• Describe the efficacy and safety at the recommended phase 2 doses.
• Key eligibility criteria
• Adults with measurable MM
• Phase 1: progression on or intolerance to all established therapies; ECOG performance status (PS) of 0 or 1
• Phase 2: at least 3 prior lines of therapy that included at least 1 protease inhibitor, at least 1 immunomodulatory imide drug (IMiD), and at least 1 anti‑CD38 antibody; ECOG PS of 0 to 2

Results

• ORR was similar for patients treated once weekly (n = 143) and those treated every 2 weeks (n = 145).
  • Triple class­–refractory: dosing once weekly, 72.6%; dosing every other week, 71.0%
  • Penta-drug refractory: dosing once weekly, 71.4%; dosing every other week,70.6%
  • The ORR was consistent across subgroups (eg, those with baseline International Staging System stage III disease, baseline cytogenetic risk, number of prior therapies, and belantamab exposure), except among patients with baseline plasmacytomas.
• Treatment at both doses led to durable responses.
• Median duration of response was not reached for those patients who achieved a complete response or better.

Conclusions

• Talquetamab, a novel agent directed against a new antigen target in myeloma, demonstrated an ORR of 73% to 74% with dosing once weekly and every other week, respectively, in a heavily pretreated group of patients.
• In those with prior T-cell redirection therapy, a 63% ORR was observed.
• Safety and pharmacokinetic/pharmacodynamic activity were consistent between groups treated once weekly and those treated every other week.
• Median duration of response (DOR) was 9 months or more in all groups, with longer DOR noted among those achieving a complete response or better.
• Overall, a low rate of discontinuations due to adverse events (AEs) was observed; the most common AEs included cytokine release syndrome, effects related to skin or nails, and dysgeusia.
• An ongoing phase 3 study (NCT05455320) is evaluating talquetamab vs approved therapies; additional phase 1 studies are evaluating combinations with other agents, including teclistamab, daratumumab, IMiDs, and/or a checkpoint inhibitor.

Chari A, Touzeau C, Schinke C, et al. 157 Talquetamab, a G protein-coupled receptor family C group 5 member D × CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: phase 1/2 results from MonumenTAL-1. Abstract presented at: 2022 American Society of Hematology Annual Meeting; December 10-13, 2022; New Orleans, LA. Abstract 157. https://ash.confex.com/ash/2022/webprogram/Paper159707.html