Talquetamab-tgvs Granted Accelerated Approval for Relapsed/Refractory Multiple Myeloma
The FDA has granted accelerated approval to talquetamab-tgvs (Talvey™, Janssen Biotech, Inc.) 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.
Why it matters: "G protein–coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells," wrote Ajai Chari, Director of the Clinical Research in Multiple Myeloma Program at the Icahn School of Medicine, Mount Sinai, and colleagues, in their published phase 1 results of the MonumenTAL-1 trial (NCT03399799, NCT4634552), on which accelerated approval was based. "Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells."
What they studied: Safety and efficacy were studied in the phase 1, open-label, multicenter, dose-escalation trial of talquetamab-tgvs in which 187 patients—who previously received at least four systemic therapies—received either 0.4 mg/kg of talquetamab-tgvs subcutaneously weekly (n=100), following two step-up doses in the first week, or 0.8 mg/kg of talquetamab-tgvs subcutaneously biweekly (n=87), after three step-up doses. Patients continued treatment until disease progression or unacceptable toxicity.
The primary end points measured were overall response rate and duration of response as assessed by an Independent Review Committee using International Myeloma Working Group (IMWG) criteria.
What they found: Of the 100 patients who received 0.4 mg/kg of talquetamab-tgvs weekly, the overall response rate was 73% with a median duration of response of 9.5 months. Of the 87 patients who received 0.8 mg/kg of talquetamab-tgvs biweekly, the overall response rate was 74% and the median duration of response was not estimable in this group. Response was maintained for a minimum of 9 months in 85% of responders.
Adverse events: The most common adverse events reported in ≥20% of the safety population (n=339) were cytokine release syndrome (CRS), dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
What to know: Please refer to the prescribing information for a Boxed Warning detailing the risk for life-threatening or fatal CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Due to these potential risks, talquetamab-tgvs is only available through a restricted program known as Tecvayli-Talvey™ Risk Evaluation and Mitigation Strategy (REMS).
What's next: Further study and evaluation of talquetamab-tgvs is ongoing for this indication to be granted regular approval.
Conclusion: "Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma," concluded Dr. Chari and colleagues.
Instructions: The recommended dosage of talquetamab-tgvs is either 0.4 mg/kg weekly or 0.8 mg/kg biweekly. Please review the prescribing information for the full dosing schedules.
For More Information
Chari A, Minnema MC, Berdeja JG, et al (2022). Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med, 387(24):2232-2244. DOI:10.1056/NEJMoa2204591
Schinke CD, Touzeau C, Minnema MC, et al (2023). Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_16). Abstract 8036. DOI:10.1200/JCO.2023.41.16_suppl.8036
Clinicaltrials.gov (2023). Dose escalation study of talquetamab in participants with relapsed or refractory multiple myeloma (MonumenTAL-1). NLM identifier: NCT03399799.
Talvey™ (talquetamab-tgvs) prescribing information (2023). Janssen Biotech, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf
US Food and Drug Administration (2023). FDA grants accelerated approval to talquetamab-tgvs for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-talquetamab-tgvs-relapsed-or-refractory-multiple-myeloma
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