FDA Approves Bi-weekly Teclistamab Dosing for Relapsed/Refractory Multiple Myeloma

FDA

The FDA has approved a supplemental Biologics License Application (sBLA) for teclistamab-cqyv (Tecvayli) at a reduced dose of 1.5 mg/kg every 2 weeks in patients with relapsed/refractory multiple myeloma who have achieved and maintained a complete response (CR) or greater for at least 6 months.¹

The approval is based on findings from the phase 1/2 MajesTEC-1 study (NCT03145181; NCT04557098), in which patients were initially treated with the recommended phase 2 dose (RP2D) of 1.5 mg/kg weekly teclistamab given subcutaneously. Patients who achieved a confirmed CR or better for at least 6 months were eligible for the reduced dose frequency until disease progression or unacceptable toxicity.

Specifically, results showed that at a median follow-up of 14.1 months, the overall response rate with the reduced dosing frequency was 63.0%, with a 39.4% CR rate or better.² A total 26.7% of patients had no minimal residual disease (MRD), and the MRD-negativity rate in those with a CR or better was 46%. The median duration of response was 18.4 months (95% CI, 14.9-not estimable).

"Tecvayli is the only BCMA-targeted immune-based therapy with weight-based dosing. Today's approval of biweekly dosing for eligible patients will further enable clinicians to meet the individual needs of patients who may want flexibility in their dosing schedules," Rachel Kobos, MD, vice president, Oncology Research & Development, Johnson & Johnson Innovative Medicine, the developer of teclistamab, stated in a news release. "As the first bispecific approved for the treatment of multiple myeloma, combined with the longest in-market experience by physicians, Tecvayli is another example of our commitment to pioneering cutting-edge research to help improve outcomes for patients with multiple myeloma."

In October 2022, the FDA granted accelerated approval to teclistamab for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³

In the single-arm, open-label, multicohort, multicenter dose-escalation MajesTEC-1 study, investigators evaluated the efficacy and safety of teclistamab in 165 adult patients with relapsed/refractory multiple myelo,a who received at least 3 prior lines of therapy.

The phase 1 portion of the trial, which was conducted with a dose escalation component (part 1) and a dose expansion component (part 2), explored the safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab in this patient population. Meanwhile, the phase 2 portion evaluated the efficacy of teclistamab at the recommended phase 2 dose of subcutaneous 1.5 mg/kg weekly.

Additional findings showed that the median progression-free survival was 11.3 months (95% CI, 8.8-17.1).

Regarding safety, the most common adverse effects included cytokine release syndrome (any-grade, 72.1%; grade 3, 0.6%), neutropenia (any-grade, 70.9%; grade 3/4, 64.2%), anemia (any-grade, 52.1%; grade 3/4, 37.0%), and thrombocytopenia (any-grade, 40.0%; grade 3/4, 21.2%). Any-grade and grade 3/4 infections occurred in 76.4% and 44.8% of patients, respectively. Neurotoxic events occurred in 14.5%, which included grade 1/2 immune effector cell–associated neurotoxicity syndrome in 5 patients.

References

1. TECVAYLI

1. (teclistamab-cqyv) biweekly dosing approved by the U.S. FDA for the treatment of patients with relapsed or refractory multiple myeloma. Johnson & Johnson. News release. February 20, 2024. Accessed February 20, 2024. https://www.prnewswire.com/news-releases/tecvayli-teclistamab
2. Moreau P, Garfall AL, van de Donk, N WCJ. Teclistamab in relapsed or refractory multiple myeloma. N Eng J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478
3. FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma. News release. FDA. October 25, 2022. Accessed October 25, 2022. https://bit.ly/3f3HffB