On 9 August 2023, the US Food and Drug Administration (FDA) granted accelerated approval to talquetamab-tgvs (Talvey, Janssen Biotech, Inc.) 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.

Full prescribing information for Talvey is available here.

Efficacy was evaluated in MMY1001 (MonumenTAL-1) (NCT03399799, NCT4634552), a single-arm, open-label, multicentre study that included 187 patients who had previously received at least four prior systemic therapies. Patients received talquetamab-tgvs 0.4 mg/kg subcutaneously weekly, following two step-up doses in the first week of therapy, or talquetamab-tgvs 0.8 mg/kg subcutaneously biweekly (every 2 weeks), following three step-up doses, until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) and duration of response (DoR) as assessed by an Independent Review Committee using IMWG criteria. The primary efficacy population consisted of patients who had previously received at least 4 prior lines of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. ORR in the 100 patients receiving 0.4 mg/kg weekly was 73% (95% confidence interval [CI] 63.2%, 81.4%) and median DoR was 9.5 months (95% CI 6.5, not estimable). ORR in the 87 patients receiving 0.8 mg/kg biweekly was 73.6% (95% CI 63%, 82.4%) and median DoR was not estimable. An estimated 85% of responders maintained response for at least 9 months.

The prescribing information for talquetamab-tgvs has a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Because of the risks of CRS and neurologic toxicity, including ICANS, talquetamab-tgvs is available only through a restricted programme 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 CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhoea.

The recommended talquetamab-tgvs dose is either 0.4 mg/kg weekly or 0.8 mg/kg biweekly. See the prescribing information for the full dosing schedules.

This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence (OCE). Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, 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 designation, and orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Faciliate.