On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.) 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 (TECVAYLI) is a T-cell redirecting IgG4λ bispecific antibody recognizing BCMA on target cells and CD3e on T cells. Generated from Ligand’s transgenic mouse (OmniAb) and Genmab’s DuoBody technology, the Fc was engineered with the stabilizing S228P mutation and L234A/L235A mutations to minimize its effector functions. Teclistamab was granted Orphan Drug designations for the treatment of MM in both the US and EU, and received the Breakthrough Therapy designation for the treatment of relapsed or refractory MM (RRMM) by the FDA, and a PRIority MEdicines (PRIME) designation by the EMA for treatment of adult patients with RRMM who previously received ≥3 prior lines of therapy. TECVAYLI (teclistamab) was granted conditional marketing authorization in the EU as monotherapy for the treatment of adult RRMM patients who previously received ≥3 prior lines of therapy in August 2022.
The authorizations for marketing were based on the results from the multicohort, open-label, Phase 1 and Phase 2 MajesTEC-1 studies (NCT03145181, NCT04557098, respectively), evaluating the safety and efficacy of teclistamab in adults with RRMM. The ongoing first-in-human dose escalation and dose expansion clinical study (NCT03145181) is assessing the efficacy of teclistamab in patients with RRMM, with the antibody administered IV (range: 0.3−19.2 μg/kg [once every 2 weeks] or 19.2−720 μg/kg [once per week]) or subcutaneously (range: 80−3000 μg/kg [once per week]) in different cohorts, with step-up dosing for 38.4 μg/kg or higher doses. Based on the dose escalation data, in the Phase 2 portion of the study patients received a weekly subcutaneous dose of teclistamab (1.5 mg/kg), after receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg. Results of the MajesTEC-1 study showed that teclistamab induced durable responses that deepened over time in patients with triple-class exposed RRMM (n=165), with an overall response rate of 63%, including a complete response in 39.4% of the patients. The median duration of response and duration of progression-free survival were 18.4 months (95% confidence interval [CI], 14.9 to not estimable) and 11.3 months (95% CI, 8.8 to 17.1), respectively. Adverse events were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1/2.
