Skip to main content

FDA Accelerated the Approval of Talvey, First Bispecific GPRC5D-Directed CD3 T-Cell Engager, for Relapsed or Refractory MM

Web Exclusives - FDA Approvals

On August 9, 2023, the FDA accelerated the approval of talquetamab-tgvs (Talvey; Janssen Biotech) for the treatment of relapsed or refractory multiple myeloma (MM) in adults who have received ≥4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

The FDA granted talquetamab priority review and breakthrough and orphan drug designations for this indication.

Talquetamab subcutaneous injection is a first-in-class bispecific GPRC5D-directed CD3 T-cell engager. This T cell–engaging antibody binds to the CD3 receptor on the surface of T cells and GPRC5D that is expressed on the surface of MM cells.

The FDA approved this indication based on the efficacy results of 2 phases of the MMY1001 (MonumenTAL-1) clinical trial (phase 1, NCT03399799; phase 2, NCT4634552), a single-arm, open-label, multicenter study that included 187 patients who had received ≥4 systemic therapies, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

Patients received talquetamab 0.4 mg/kg subcutaneously weekly after 2 step-up doses in the first week of therapy, or talquetamab 0.8 mg/kg subcutaneously every 2 weeks after 3 step-up doses, until disease progression or unacceptable adverse events.

The main efficacy outcomes were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee using the International Myeloma Working Group criteria. The primary efficacy population included patients who had received ≥4 lines of therapies, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.

In the 100 patients who received 0.4 mg/kg weekly, the ORR was 73% (95% confidence interval [CI], 63.2-81.4), and the median DOR was 9.5 months (95% CI, 6.5-not estimable). Among the 87 patients receiving 0.8 mg/kg biweekly, the ORR was 73.6% (95% CI, 63-82.4) and the median DOR was not estimable. Overall, an estimated 85% of responders maintained their 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 Ajai Chari, MD, Director of the Multiple Myeloma Program and 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,” Dr Chari added.

In the same press release, Michael Andreini, President and Chief Executive Officer of the Multiple Myeloma Research Foundation, observed, “Although options for the treatment of MM have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options,” adding that the “approval of talquetamab provides patients with a new treatment approach for relapsed or refractory disease.”

The prescribing information for talquetamab has a boxed warning about the serious adverse events associated with this new drug, including life-threatening or fatal cytokine release syndrome (CRS) and neurologic events, including immune effector cell–associated neurotoxicity syndrome (ICANS). Because of the risks for CRS and neurologic adverse events, including ICANS, talquetamab is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called the Tecvayli-Talvey REMS.

The most common (≥20%) adverse events reported in the 339 patients in the safety population were CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.

The recommended dose of talquetamab is 0.4 mg/kg weekly or 0.8 mg/kg biweekly subcutaneous injections after an initial step-up phase to determine the optimal dosing regimen for each patient. For complete dosing schedules, consult the prescribing information for talquetamab.

Continued FDA approval for this indication may be contingent on confirmatory trials that verify and describe the clinical benefit of talquetamab.

Related Items
Directory of FDA Approvals, August Through December 2023
December 2023 Vol 16, Payers' Guide to FDA Updates published on January 26, 2024 in FDA Approvals
Iwilfin FDA Approved for Adults and Pediatric Patients with High-Risk Neuroblastoma
Web Exclusives published on January 16, 2024 in FDA Approvals
Welireg Now FDA Approved for Patients with Advanced Renal Cell Carcinoma
Web Exclusives published on January 16, 2024 in FDA Approvals
Ogsiveo First Treatment FDA Approved for Desmoid Tumors
Web Exclusives published on January 2, 2024 in FDA Approvals
Keytruda Plus Chemotherapy Receives New FDA Approvals for Advanced Biliary Tract Cancer and 2 Forms of Advanced Gastroesophageal Junction Adenocarcinoma
Web Exclusives published on December 18, 2023 in FDA Approvals
Last modified: September 9, 2023