J&J submits application to EMA for TECVAYLI (teclistamab) in combination with DARZALEX (daratumumab) subcutaneous formulation for patients with relapsed/refractory multiple myeloma in second line
Johnson & Johnson announced on January 6, 2026 the submission of a Type II variation application to the European Medicines Agency (EMA) seeking approval for an indication extension of TECVAYLI(teclistamab) in combination with DARZALEX subcutaneous (daratumumab SC) formulation for the treatment of adult patients with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior therapy.
The combination of teclistamab and daratumumab SC work in a complementary manner by targeting both BCMA and CD38 to prime and activate the immune system, supporting the potential to improve patient outcomes by enhancing immune-mediated response earlier in the treatment journey.
The submission is supported by data from the Phase 3 MajesTEC-3 study. The study enrolled 587 patients across two treatment arms: teclistamab and daratumumab SC versus daratumumab SC and dexamethasone with either pomalidomide or bortezomib (DPd/DVd). Results show an 83.4 percent reduction in the risk of disease progression or death compared to standard regimens at nearly three years follow-up (hazard ratio [HR], 0.17; 95 percent confidence interval [CI], 0.12-0.23; P<0.0001). More than 90 percent of patients who remained progression-free at six months (n=249) remained progression-free at three years. In the study, teclistamab plus daratumumab SC and standard of care comparators had similar rates of Grade 3/4 (95.1 percent vs. 96.6 percent) treatment-emergent adverse events (TEAE) Most common Grade 3/4 events were cytopenia and infection.1 Infections were observed with teclistamab and daratumumab SC (any grade, 96.5 percent; Grade 3/4, 54.1 percent) and DPd/DVd comparator (any grade, 84.1 percent; Grade 3/4, 43.4 percent).
Based on the statistical significance of the results, the Independent Data Monitoring Committee (IDMC) recommended unblinding of the study. Data from the MajesTEC-3 study were recently presented as a late-breaking oral presentation at the 2025 American Society of Hematology (ASH) Annual Meeting, with simultaneous publication in The New England Journal of Medicine.
Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) for the use of teclistamab and daratumumab SC in combination as a treatment for RRMM to the U.S. Food and Drug Administration (FDA). The FDA has granted Breakthrough Therapy Designation for the combination regimen, which allows for expediting the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).
About the MajesTEC-3 Study
MajesTEC-3 (NCT05083169) is an ongoing, Phase 3 randomised study evaluating the safety and efficacy of teclistamab plus daratumumab subcutaneous (SC) (n=291) versus investigator’s choice of daratumumab subcutaneous (SC) and dexamethasone with either pomalidomide or bortezomib (n=296) (DPd/DVd) in patients with relapsed/refractory multiple myeloma (RRMM) who have received 1–3 prior lines of therapy. The primary endpoint is progression-free survival (PFS) and secondary endpoints include complete response or better (≥CR), overall response rate (ORR), minimal residual disease (MRD) negativity (10⁻⁵ by next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. The MajesTEC-3 study is a part of the MajesTEC clinical programme, which includes exploring the potential of teclistamab as a combination regimen.
About TeclistamabTeclistamab received European Commission (EC) approval in August 2022 for the treatment of patients with RRMM who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. In August 2023, the EC approved a Type II variation application for teclistamab, providing the option for a reduced dosing frequency of 1.5mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months.
Teclistamab is an off-the-shelf (or ready-to-use) bispecific antibody. Teclistamab, a subcutaneous injection, redirects T-cells through two cellular targets (BCMA and CD3) to activate the body’s immune system to fight cancer. Teclistamab is currently being evaluated in several combination studies.
About Daratumumab and Daratumumab SC
In August 2012, Janssen Biotech, Inc., a Johnson & Johnson company, and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 618,000 patients worldwide. Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.
CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death. Daratumumab may also have an effect on normal cells. Data across ten Phase 3 clinical trials, in both the frontline and relapsed settings across all newly diagnosed multiple myeloma patients,, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.