Talquetamab further investigated in heavily pre-treated MM after promising phase 2 data 

Talquetamab demonstrated a favourable safety profile and promising response rates in a heavily pre-treated group of patients with multiple myeloma (MM) in the phase 1/2 MonumenTAL-1 study, even in those who received prior T-cell redirection therapy. A phase 3 study is initiated to compare this investigational agent with approved therapies.

“Talquetamab is a novel, first-in-class, T cell-redirecting, bispecific antibody, targeting the antigen GPRC5D,” said Prof. Ajai Chari (Mount Sinai School of Medicine, NY, USA) [1]. In the phase 1 part of the MonumenTAL-1 study (NCT03399799), talquetamab showed an overall response rate (ORR) of 64–70% in patients with relapsed/refractory MM [1,2]. Prof. Chari presented the results of the phase 2 part of MonumenTAL-1, including 288 patients with MM who had received at least 3 prior lines of therapy and of a cohort of patients who had received prior T-cell redirection therapy (NCT04634552; n=51). Participants were randomised 1:1 to either 0.4 mg/kg talquetamab every week or to a dose of 0.8 mg/kg bi-weekly.

In participants who were triple-class refractory, the ORRs were 72.6% and 71.0% for once weekly dosing and bi-weekly dosing, respectively. Similarly, in penta-drug-refractory participants, the corresponding ORRs were 71.4% and 70.6%. Furthermore, the ORRs in the cohort of participants who had received prior T-cell redirection therapy were 72.2% for those who had received prior CAR-T therapy (n=36) and 44.4% for those who had received prior bispecific antibody therapy (n=18).

As for safety, grade 3/4 anaemia, neutropenia, lymphopenia, and thrombocytopenia were reported in approximately 20–30% of participants in both dosing groups. Prof. Chari commented that cytopenia was generally limited to the first few cycles. Also, grade 3/4 infections occurred in 11.7–16.8% of the participants. Rates of non-haematological adverse events (AEs) of grade 3 or 4 were not higher than 3.5% for a specific event. The most common any-grade AEs were cytokine release syndrome (CRS; 79.0%), skin-related AEs (55.9%), and nail-related AEs (51.7%). “The CRS events were mostly of grade 1 or 2 and occurred predominantly during the step-up phase or during the administration of the first full dose,” added Prof. Chari.

Talquetamab showed a manageable safety profile and encouraging efficacy results in the current phase 1/2 study. “The lack of an infection profile and cytopenia make this investigational drug an ideal candidate to combine with other agents,” argued Prof. Chari. The phase 3 MonumenTAL-3 study (NCT05455320) will investigate talquetamab in combination with daratumumab and pomalidomide or talquetamab in combination with daratumumab versus daratumumab, pomalidomide, and dexamethasone.

1. Chari A, et al. 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. Abstract 157, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.
2. Minnema M, et al. J Clin Oncol. 2022;40(16_suppl):8015–8015.

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Posted on 20 February 2023