Talquetamab demonstrated a favorable 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 to 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)1 at the 2022 annual meeting of the American Society of Hematology. In the phase 1 part of the MonumenTAL-1 study, talquetamab showed an overall response rate (ORR) of 64% to 70% in patients with relapsed/refractory MM.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 (N=51). Participants were randomized 1:1 to either 0.4 mg/kg talquetamab every week, or to a dose of 0.8 mg/kg bi-weekly.

In patients 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 patients, the corresponding ORRs were 71.4% and 70.6%. Furthermore, the ORRs in the cohort of patients 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% to 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% to 16.8% of 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 (79.0%), skin-related AEs (55.9%), and nail-related AEs (51.7%).

The phase 3 MonumenTAL-3 study will investigate talquetamab in combination with daratumumab and pomalidomide and talquetamab in combination with daratumumab, respectively, with daratumumab in combination with pomalidomide and dexamethasone.

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