Updated phase 2 results of the MonumenTAL-1 study showed promising efficacy and a tolerable safety profile with talquetamab, a novel T-cell–redirecting bispecific antibody, in patients with RRMM.
Talquetamab is a novel, first-in-class, T-cell–redirecting bispecific antibody that targets both GPRC5D and CD3 receptors. GPRC5D is highly expressed in malignant cells; however, its limited expression in human tissue makes it an optimal target for patients with multiple myeloma (MM). MonumenTAL-1 is a phase 1/2 study investigating talquetamab in patients with relapsed/refractory MM (RRMM). Phase 1 of the study identified 2 recommended phase 2 doses (RP2Ds) for talquetamab: 0.4 mg/kg subcutaneous (SC) weekly (QW) and 0.8 mg/kg SC every other week (Q2W), which achieved an overall response rate (ORR) of 64%-70% in the published phase 1 results. At the 2022 American Society of Hematology meeting, Ajai Chari presented the pivotal phase 2 results in a cohort of patients with prior chimeric antigen receptor (CAR) T-cell or bispecific antibody treatment.
Patients in phase 2 received more than 3 lines of prior therapy. There were 3 cohorts included: patients receiving talquetamab at 0.4 mg/kg QW (122 patients in phase 2), 0.8 mg/kg Q2W (109 patients in phase 2), and patients with prior T-cell redirection therapy at either dose (34 patients in phase 2). In patients treated with 0.4 mg/kg QW, the ORR was 74%, and a very good partial response or better (≥VGPR) was achieved in 59%. In patients treated with 0.8 mg/kg Q2W, the ORR was 73.1% with a ≥VGPR in 57%. In triple-class refractory patients, the ORR was 72.6% and 71% in the QW and Q2W cohorts, respectfully. ORR was consistent across subgroups including baseline International Staging System stage III, cytogenetic risk, and prior number of therapies. In patients treated with 0.4 mg/kd QW, the median time to response was 1.2 months and median time to best response was 2.1 months. In patients treated with 0.8 mg/kg Q2W, median time to first response was 1.3 months and median time to best response was 2.7 months. Median progression-free survival was 7.5 months and 11.9 months in QW and Q2W patients, respectively. In patients with prior T-cell redirection, ORR was 62.7%, 72.2% in patients with prior CAR T-cell therapy, and 44.4% in patients with prior bispecific antibody treatment. High-grade adverse events (AEs) were uncommon, were mostly hematologic when they occurred, and occurred early in treatment. Grade 3 and 4 infections were low, 16.8% and 11.7% with QW and Q2W, respectively. The most common AE with both RP2Ds was cytokine release syndrome, with a majority of cases grade 1 or 2. Other common AEs were dysgeusia, anemia, and skin-related AEs and were able to be managed. Immune effector cell–associated neurotoxicity syndrome occurred in 10% to 11% of patients across RP2D groups, most were grade 1 and 2, and most were resolved. Safety was comparable in patients with prior T-cell redirection therapy.
Talquetamab demonstrated promising efficacy and a manageable safety profile in heavily pretreated patients with RRMM. Additional studies are currently underway evaluating talquetamab in combination strategies.
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