On 25 October 2022, the US Food and Drug Administration (FDA) granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.), the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Teclistamab-cqyv was evaluated in MajesTEC-1 (NCT03145181; NCT04557098), a single-arm, multi-cohort, open-label, multicentre study. The efficacy population consisted of 110 patients who had previously received at least 3 prior treatments, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and had not received prior BCMA-targeted treatment.

The main efficacy outcome measure was overall response rate (ORR) as determined by the Independent Review Committee assessment using International Myeloma Working Group 2016 criteria. ORR was 61.8% (95% confidence interval [CI] 52.1, 70.9). With a median follow-up of 7.4 months among responders, the estimated duration of response rate was 90.6% (95% CI 80.3%, 95.7%) at 6 months and 66.5% (95% CI 38.8%, 83.9%) at 9 months.

The prescribing information for teclistamab-cqyv has a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received teclistamab-cqyv at the recommended dose, CRS occurred in 72% of patients, neurologic toxicity in 57%, and ICANS in 6%. Grade 3 CRS occurred in 0.6% of patients and Grade 3 or 4 neurologic toxicity occurred in 2.4%.

Because of the risks of CRS and neurologic toxicity, including ICANS, teclistamab-cqyv is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli REMS.

The most common adverse reactions (≥20%) occurring in the 165 patients in the safety population, were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhoea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased haemoglobin, and decreased platelets.

The recommended teclistamab-cqyv dose is 0.06 mg/kg via subcutaneous injection on Day 1, 0.3 mg/kg on Day 4, and 1.5 mg/kg on Day 7, followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.

Full prescribing information for Tecvayli is available here.

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, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews may be 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 and breakthrough 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 Facilitate.