Phase 2 MonumenTAL-1 Results of Talquetamab

The GPRC5DxCD3 bispecific antibody's role in relapsed refractory multiple myeloma

Dr. Carolina Schinke presented results on the updated findings of talquetamab in patients with relapsed or refractory multiple myeloma. Talquetamab is an off-the-shelf, first-in-class bispecific antibody targeting the novel antigen GPRC5D. The study included patients who were intolerant to or had progressed on established therapies, with some patients having received prior T-cell redirection therapy. The primary endpoint was the overall response rate, and the results showed promising outcomes with high response rates and durable responses. Adverse events were generally manageable, with low rates of treatment discontinuation due to side effects. These findings support further investigation of talquetamab, including its use in combination therapies.

• Talquetamab is an off-the-shelf bispecific antibody targeting the novel antigen GPRC5D.
• The study included patients with relapsed or refractory multiple myeloma who were intolerant to or had progressed on established therapies.
• The primary endpoint of the study was the overall response rate.
• Overall response rates were over 70% in the pivotal cohorts, with approximately 60% of patients achieving very good partial response or better.
• Patients who received prior T-cell redirection therapy had an overall response rate of 64.7%, with 55% achieving very good partial response or better.
• Overall response rates were consistent across clinically relevant subgroups, except in patients with Baseline plasmacytomas.
• The 12-month duration of response rate in patients who achieved complete response or better was 79% or greater across the cohorts.
• The 12-month progression-free survival rate ranged from 35% to 54% across the cohorts.
• The 12-month overall survival rate was 63% or greater across all cohorts.
• Common adverse events included cytokine release syndrome, viscosia, and skin and nail-related events.
• Low rates of treatment discontinuation due to adverse events were observed, including those related to skin and nail events and dysgeusia.
• Most high-grade adverse events were cytopenias, primarily occurring in the first few treatment cycles.
• Grade 3-4 infections were below 30%, with discontinuations due to infections at 2% or below.
• Anti-drug antibodies were detected in 20% to 35% of patients but did not impact the pharmacokinetics, safety, or efficacy of talquetamab.

Authors:
Carolina D. Schinke, Cyrille Touzeau, Monique C. Minnema, Niels W.C.J. van de Donk, Paula Rodríguez-Otero, Maria-Victoria Mateos, Leo Rasche, Jing Christine Ye, Deeksha Vishwamitra, Xuewen Ma, Xiang Qin, Michela Campagna, Tara J. Masterson, Brandi Hilder, Jaszianne A. Tolbert, Thomas Renaud, Jenna Goldberg, Christoph Heuck, Ajai Chari

Clinical trial information: NCT03399799, NCT04634552