First-in-Class Drug Approved for Heavily Pretreated Myeloma

— Talquetamab achieved response rate of over 70% in MonumenTAL-1 study

MedicalToday
FDA APPROVED talquetamab (Talvey) over a computer rendering of a spine and multiple myeloma cells

The FDA granted for treating adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, drug developer Janssen announced Thursday.

The first-in-class bispecific T-cell-engaging antibody against CD3 and GPRC5D was approved as a weekly or biweekly subcutaneous injection after an initial step-up phase.

Approval was based on 187 patients from MonumenTAL-1 -- a -- who had received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and had no previous exposure to T-cell redirection therapy.

The study -- which assessed the drug at different dosing regimens -- showed that patients treated at a biweekly dose of 0.8 mg/kg achieved an overall response rate of 73.6%. With a median follow-up of nearly 6 months from first response, 58% of patients achieved a very good partial response (VGPR) or better, including 33% who achieved a complete response or better.

At the weekly dose of 0.4 mg/kg, 73% of patients achieved an overall response. With a median follow-up of nearly 14 months from first response, 57% of patients achieved a VGPR or better, including 35% who achieved a complete response or better.

Median duration of response was not reached in the 0.8 mg/kg biweekly dose group, and was 9.5 months in the 0.4 mg/kg weekly dose group. Among patients receiving the 0.8 mg/kg biweekly dose, an estimated 85% of responders maintained response for at least 9 months.

The study also included 32 patients exposed to prior bispecific antibody or chimeric antigen receptor (CAR) T-cell therapy (94% with B-cell maturation antigen [BCMA]-directed therapy) who received talquetamab at the 0.4 mg/kg weekly dose. At a median follow-up of 10.4 months, 72% achieved an overall response, with an estimated 59% maintaining the response for at least 9 months.

"The clinically meaningful efficacy and safety profile observed with talquetamab in heavily pretreated patients in this clinical trial, which included patients treated with prior BCMA-targeted bispecific or CAR T-cell therapy, has been notable," said study investigator Ajai Chari, MD, of the University of California San Francisco, in the press release. "Patients at this stage of disease have a poor prognosis. Talquetamab as a first-in-class therapy is a new option for patients with this difficult-to-treat blood cancer."

for talquetamab includes a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. Because of these risks, talquetamab will only be available through a risk evaluation and mitigation strategy (REMS) program.

In trials, the most common adverse reactions (≥20%) were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight reductions, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common grade 3/4 laboratory abnormalities (≥30%) reported included decreases in lymphocyte counts, neutrophil counts, white blood cell counts, and hemoglobin.

The most common non-hematologic adverse events seen in the study were oral toxicities, which occurred in 80% of patients, with grade 3 events occurring in 2.1% of patients.

Serious infections occurred in 16% of patients, with fatal infections occurring in 1.5%.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.