Talvey Gets Accelerated Approval for Difficult-to-Treat Multiple Myeloma

The Food and Drug Administration (FDA) has granted accelerated approval to Talvey^™ (talquetamab-tgvs) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

Talvey is a bispecific G protein-coupled receptor class C group 5 member D (GPRC5D)-directed CD3 T-cell engager. In vitro, talquetamab-tgvs activated T-cells caused the release of proinflammatory cytokines and resulted in the lysis of multiple myeloma cells.

The accelerated approval was based on response rate and durability of response observed in the MonumenTAL-1 study (ClinicalTrials.gov Identifier: NCT03399799, NCT04634552). The trial included patients who had previously received at least 3 prior systemic therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Efficacy outcome measures included overall response rate (ORR) and duration of response (DOR).

Treatment was administered as a subcutaneous (SC) injection either on a weekly (0.4mg/kg) or biweekly (0.8mg/kg) schedule. Results were reported for 187 patients treated with Talvey who were not exposed to prior T cell reduction therapy and who had received at least 4 prior lines of therapy.

Among patients who received weekly therapy (n=100), ORR was 73% (95% CI, 63.2-81.4), with 26% of patients having a stringent complete response, 9% having a complete response, 22% having a very good partial response, and 16% having a partial response. Median time to first response was 1.2 months (range, 0.2-10.9) and median DOR was 9.5 months (6.5, not estimable). Median duration of follow-up from first response among responders was 13.8 months (range, 0.8-15.4).

Among participants who received biweekly treatment (n=87), ORR was 73.6% (95% CI, 63-82.4), with 20% of patients having a stringent complete response, 13% having a complete response, 25% having a very good partial response, and 16% having a partial response. Median time to first response was 1.3 months (range, 0.2-9.2) and median DOR was not estimable. Median duration of follow-up from first response among responders was 5.9 months (range, 0-9.5). Among responders, 85% maintained response for at least 9 months.

The study also included 32 patients who were exposed to prior bispecific antibody or CAR-T cell therapy and had received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. These patients received 0.4mg/kg SC weekly. Median duration of follow-up was 10.4 months, with 72% (95% CI, 53-86) of patients achieving ORR; 59% of responders maintained response for at least 9 months.

The most common adverse reactions reported with Talvey were pyrexia, cytokine release syndrome (CRS), dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. Grade 3 or 4 laboratory abnormalities included decreased lymphocyte count, neutrophil count, white blood cells, and hemoglobin.

The prescribing information for Talvey includes a Boxed Warning regarding the risk of CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. Because of these risks, Talvey is only available through a restricted program called the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS). Patients should be hospitalized for 48 hours after administration of all doses with the Talvey step-up dosing schedule.

Talvey is supplied as a ready-to-use solution in 3mg/1.5mL (2mg/mL) and 40mg/mL single-dose vials. It is expected to be available in the coming weeks.