On August 9, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the bispecific antibody talquetamab-tgvs (Talvey) for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).
Talquetamab is a first-in-class, off-the-shelf, T-cell–redirecting bispecific antibody that targets not only CD3 receptors but also G protein–coupled receptor family C group 5 member D (GPRC5D). GPRC5D is highly expressed on malignant plasma cells but rarely in normal human tissue.
MMY1001 (MonumenTAL-1) Trial
Efficacy was evaluated in MMY1001 (MonumenTAL-1; ClinicalTrials.gov identifier NCT03399799), a single-arm, open-label, multicenter study that included 187 patients with multiple myeloma who had previously received at least four prior systemic therapies. Patients received either talquetamab at 0.4 mg/kg subcutaneously weekly following two step-up doses in the first week of therapy or talquetamab at 0.8 mg/kg subcutaneously biweekly following three step-up doses, until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response, as assessed by an independent review committee using International Myeloma Working Group criteria. The primary efficacy population consisted of patients who had previously received at least four prior lines of therapies (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).
Overall response rate in the 100 patients receiving 0.4 mg/kg weekly was 73% (95% confidence interval [CI] = 63.2%–81.4%), and median duration of response was 9.5 months (95% CI = 6.5 months to not estimable). Overall response rate in the 87 patients receiving 0.8 mg/kg biweekly was 73.6% (95% CI = 63%–82.4%), and median duration of response was not estimable. An estimated 85% of responders maintained their response for at least 9 months.
The prescribing information for talquetamab has a boxed warning for life-threatening or fatal cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Because of the risks of cytokine-release syndrome and neurologic toxicity, including ICANS, talquetamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS.
The most common adverse reactions reported in the 339 patients in the safety population (≥ 20%) were cytokine-release syndrome, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
The recommended talquetamab dose is either 0.4 mg/kg weekly or 0.8 mg/kg biweekly.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for the concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review, Breakthrough Therapy, and Orphan Drug designations.
