On October 25, 2022, 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.
Teclistamab-cqyv was evaluated in MajesTEC-1 (NCT03145181; NCT04557098), a single-arm, multicohort, open-label, multicenter study. The efficacy population consisted of 110 patients who had 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 (ORR) as determined by the independent review committee assessment using International Myeloma Working Group 2016 criteria. ORR was 61.8% (95% CI = 52.1, 70.9). The estimated duration of response rate was 90.6% (95% CI = 80.3%, 95.7%) at six months and 66.5% (95% CI = 38.8%, 83.9%) at nine months, with a median follow-up of 7.4 months among responders.
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 the recommended dose of teclistamab-cqyv, CRS occurred in 72%, neurologic toxicity in 57%, and ICANS in 6%. Grade 3 or 4 neurologic toxicity occurred in 2.4% of patients and grade 3 CRS occurred in 0.6%.
Because of CRS and neurologic toxicity risks, 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 reported in at least 20% of the 165 patients in the safety population treated with teclistamab-cqyv were pyrexia, CRS, musculoskeletal pain, injection-site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common grade 3 to 4 laboratory abnormalities reported in at least 20% of patients treated with teclistamab-cqyv 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 patients experience disease progression or unacceptable toxicity.
View the full prescribing information for teclistamab-cqyv.
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the 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.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
The application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted 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 or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.