FDA Approves New Biweekly Reduced Dosing of Tecvayli Based on Phase I/II MajesTEC-1 Trial Data

Image credit: Saiful52 | stock.adobe.com. Microscopic view of bone marrow slide feature are suggestive Multiple myeloma, also known as myeloma, is a type of bone marrow cancer.

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

Tecvayli is an off-the-shelf bispecific T cell–engaging antibody that attaches to the CD3 receptor on T cells and the B-cell maturation antigen expressed on multiple myeloma cells and some healthy B-lineage cells. Tecvayli subsequently activates T cells, which leads to the release of proinflammatory cytokines and in the lysis of multiple myeloma cells.²

"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," said Rachel Kobos, MD, vice president, Oncology Research & Development, Johnson & Johnson Innovative Medicine, in a press 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."¹

The FDA based the regulatory action on findings from the Phase I/II MajesTEC-1 trial (NCT03145181; NCT04557098). Investigators enrolled patients who received prior treatment with the recommended Phase II dose (RP2D) of 1.5 mg/kg weekly subcutaneous Tecvayli. Patients were eligible for the lower dosing frequency if they showed a confirmed CR or better for at least six months until disease progression or unacceptable toxicity.

At a median follow-up of 14.1 months, the overall response rate with the lower dosing frequency was 63.0%, with a 39.4% CR rate or better.2 Further, 26.7% of patients given the lower dose showed no minimal residual disease (MRD), with a 46% MRD-negativity rate among individuals achieving a CR or better. Median duration of response in these patients was 18.4 months.

Tecvayli was granted accelerated approval by the FDA in October 2022 for adults with relapsed/refractory multiple myeloma previously administered at least four lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³

The approval was based on efficacy and safety findings for Tecvayli from the single-arm, open-label, multicohort, multicenter, dose-escalation MajesTEC-1 trial. The trial investigated the efficacy and safety of Tecvayli among 165 adults with relapsed/refractory multiple myeloma previously administered at least three lines of therapy.

Phase I of the trial included a dose escalation component (part 1) and a dose expansion component (part 2) to analyze the safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab among patients with relapsed/refractory multiple myeloma. Phase II of the trial analyzed the efficacy of the therapy at the recommended subcutaneous dose of 1.5 mg/kg administered weekly.

The results showed that median progression-free survival was 11.3 months among patients administered Tecvayli. In terms of 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%).

References

1. TECVAYLI (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 21, 2024. https://www.prnewswire.com/news-releases/tecvayli-teclistamab

2. Kumar SK, Callander NS, Adekola K, et al. Multiple myeloma, version 3.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020;18(12):1685-1717. doi:10.6004/jnccn.2020.0057. Accessed February 21, 2024.

3. FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma. News release. FDA. October 25, 2022. Accessed February 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma