Talquetamab Has ‘Highly Promising Efficacy’ in Relapsed/Refractory MM

By Kerri Fitzgerald - Last Updated: November 16, 2022

Talquetamab demonstrated “highly promising efficacy” in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), according to updated results from the MonumenTAL-1 phase I trial.

Advertisement

Monique Minnema, MD, PhD, of the University Medical Center Utrecht in the Netherlands, and colleagues conducted the trial and presented their findings at the 2022 American Society of Clinical Oncology Annual Meeting.

Talquetamab is a novel, first-in-class bispecific IgG4 antibody that binds to CD3 receptors and G protein-coupled receptor family C group 5 member D (GPRC5D), which is expressed on malignant plasma cells. The drug mediates T-cell–activated lysis of GPRC5D-positive MM cells.

The study included patients with MM who had relapsed/refractory disease or were intolerant of standard therapies. Patients who previously received B-cell maturation antigen-directed therapies were eligible for inclusion. The researchers’ primary objectives were to identify the recommended phase II dose of talquetamab and assess the drug’s safety and tolerability at the recommended phase II doses.

The researchers determined subcutaneous talquetamab 405 μg/kg once weekly (n=30) and subcutaneous talquetamab 800 μg/kg once weekly (n=44) were the recommended phase II doses.

All patients receiving talquetamab 405 μg/kg were triple-class exposed, and 77% were triple-class refractory, with a median of six prior lines of therapy. Almost all patients (98%) receiving talquetamab 800 μg/kg were triple-class exposed, and 75% were triple class refractory, with a median of five prior lines of therapy. The median follow-up was 11.7 months in patients receiving the lower dose and 4.2 months in patients receiving the higher dose.

The overall response rate in evaluable patients was 70% in the group receiving talquetamab 405 μg/kg and was 64% in the group receiving talquetamab 800 μg/kg. The very good partial response or better rate was 57% and 52%, respectively. The median time to first response was 0.9 month in the group receiving talquetamab 405 μg/kg and 1.2 months in the group receiving talquetamab 800 μg/kg.

Most adverse events were grade 1 or 2, with the most common being cytopenia and cytokine release syndrome (CRS). CRS, which “mostly occurred during step-up dosing,” was reported in 77% of patients receiving the lower dose and 80% receiving the higher dose, according to Dr. Minnema and colleagues.

Infections occurred in 47% of patients receiving the lower dose and 34% of patients receiving the higher dose. Skin-related adverse events and nail disorders occurred in 83% of patients receiving the lower dose and 75% of patients receiving the higher dose. Dysgeusia, which “was generally mild and managed with dose adjustments,” occurred in 63% of patients receiving the lower dose and 57% of patients receiving the higher dose. No deaths occurred due to drug-related adverse events.

The study showed that both recommended phase II doses of the drug “have comparable safety, efficacy, and pharmacokinetic profiles and confirm talquetamab as a novel, first-in-class therapy with highly promising efficacy” in heavily pretreated patients with relapsed/refractory MM, Dr. Minnema and colleagues concluded.

Reference

Minnema MC, Krishnan AY, Berdeja JG, et al. Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): updated results from MonumenTAL-1. J Clin Oncol. 2022;40(16_suppl):8015-8015.

Advertisement
Advertisement
Advertisement