On October 25, the U.S. Food and Drug Administration (FDA) granted accelerated approval to teclistamab-cqyv (Tecvayli), 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 therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
MajesTEC-1
Teclistamab-cqyv was evaluated in MajesTEC-1 (ClinicalTrials.gov identifiers NCT03145181 and NCT04557098), a single-arm, multicohort, open-label, multicenter study. The efficacy population consisted of 110 patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and had not received prior BCMA-targeted therapy.
The main efficacy outcome measure was overall response rate as determined by the independent review committee assessment using International Myeloma Working Group 2016 criteria. The overall response rate 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 and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Among patients who received teclistamab-cqyv at the recommended dose, cytokine-release syndrome occurred in 72% of patients, neurologic toxicity occurred in 57%, and ICANS occurred in 6%. Grade 3 cytokine-release syndrome occurred in 0.6% of patients and grade 3 or 4 neurologic toxicity occurred in 2.4%.
Because of the risks of cytokine-release syndrome 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, cytokine-release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common grade 3 to 4 laboratory abnormalities (≥ 20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, 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.
More About the FDA Approval
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the 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 also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
