FDA Grants Accelerated Approval to Talquetamab-tgvs for Patients With Heavily Pretreated Multiple Myeloma


Talquetamab-tgvs (Talvey) is a first-in-class bispecific antibody that binds to GPRC5D and CD3 to induce T cell-mediated killing of GPRC5D-expressing multiple myeloma cells.

The FDA has granted accelerated approval to talquetamab-tgvs (Talvey; Janssen Pharmaceutical Companies of Johnson & Johnson) for the treatment of adults with relapsed or refractory multiple myeloma previously administered at least 4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

The first-in-class bispecific antibody binds to G protein-coupled receptor class C group 5 member D (GPRC5D) and CD3 to induce T cell-mediated killing of GPRC5D-expressing multiple myeloma cells. Preclinical models found that talquetamab induced the death of multiple myeloma cells and inhibited tumor formation and growth.

“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 [chimeric antigen receptor (CAR)]-T cell therapy, has been notable,” said Ajai Chari, MD, director of Multiple Myeloma Program, professor of Clinical Medicine at the University of California, San Francisco, in a 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.”

Talquetamab is indicated as a weekly or biweekly subcutaneous (SC) injection following an initial step-up dosing phase. The approval was based on findings from the phase 2 MonumenTAL-1 study, which enrolled patients previously administered at least 4 lines of therapy and who were not exposed to prior T-cell redirection therapy (n=187).

The results showed meaningful overall response rates (ORR), with the SC biweekly dose of 0.8 mg/kg producing an ORR in 73.6% of patients (95% confidence interval [CI], range, 63.0 to 82.4). At a median follow-up of nearly 6 months (range, 0 to 9.5) from first response among patients who responded to therapy, 58% achieved a very good partial response (VGPR) or better, including 33% who achieved a complete response (CR) or better.

In the SC weekly dose of 0.4 mg/kg cohort, 73.0% of patients (95 percent CI, range, 63.2 to 81.4) achieved an ORR. At a median follow-up of approximately 14 months (range, 0.8 to 15.4) from the first response among patients who responded, 57% achieved a VGPR or better, including 35% of patients who achieved a CR or better.

The median duration of response was 9.5 months in the 0.4 mg/kg SC weekly dose group and was not reached in the 0.8 mg/kg SC biweekly dose cohort. In the 0.8 mg/kg SC biweekly dose cohort, approximately 85% of responders maintained that response for at least 9 months.

"Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options,” said Michael Andreini, president and chief executive officer, Multiple Myeloma Research Foundation, in a press release. “Today’s approval of talquetamab provides patients with a new treatment approach for relapsed or refractory disease that is a welcome addition to the myeloma community.”

The MonumenTAL-1 study enrolled 32 patients to receive talquetamab at the 0.4 mg/kg SC weekly dose. Patients enrolled were previously exposed to bispecific antibody or CAR T-cell therapy (94% B-cell maturation antigen [BCMA]-directed therapy) and previously administered at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. At a median duration of follow-up of 10.4 months, 72% of patients (95% CI, range, 53 to 86) achieved an ORR per an Independent Review Committee assessment. Further, approximately 59% of responders maintained the response for at least 9 months.

Talquetamab includes a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. The most commonly reported adverse events (AEs) ≥20% were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight loss, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common grade 3 or 4 laboratory abnormalities (≥30%) were reduced lymphocyte count, reduced neutrophil count, reduced white blood cell, and reduced hemoglobin.

Oral toxicities were the most common non-hematologic AE, observed in 80% of patients, with grade 3 toxicities observed in 2.1% of patients. The most frequently reported oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%) and ageusia (18%).

Further, 62% of patients experienced weight loss, with 29% experiencing grade 2 weight loss and 2.7% with grade 3 weight loss. Serious infections were reported in 16% of patients and fatal infections occurred in 1.5% of patients. Permanent discontinuation of talquetamab because of an AE occurred in 9% of patients.

Talquetamab’s accelerated approval was based on response rate and durability of response demonstrated in clinical trials, with continued approval contingent on verification and description of clinical benefit in confirmatory trials.


U.S. FDA Approves TALVEY™ (talquetamab-tgvs), a First-in-Class Bispecific Therapy for the Treatment of Patients with Heavily Pretreated Multiple Myeloma. Johnson & Johnson. News release. August 10, 2023. https://www.jnj.com/u-s-fda-approves-talvey-talquetamab-tgvs-a-first-in-class-bispecific-therapy-for-the-treatment-of-patients-with-heavily-pretreated-multiple-myeloma

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