TECVAYLI® (teclistamab) monotherapy significantly improves progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma refractory to anti-CD38 therapy and lenalidomide, based on Phase 3 MajesTEC-9 trial results (NCT05572515).
Written By: Pharmacally Medical News Desk
Johnson & Johnson has reported positive Phase 3 results showing that TECVAYLI monotherapy significantly improves both progression-free survival (PFS) and overall survival (OS) compared with standard-of-care regimens in patients with multiple myeloma treated as early as first relapse. The benefit was observed predominantly in patients whose disease was refractory to prior anti-CD38 antibody therapy and lenalidomide, representing a population with limited treatment options.
These findings are from the MajesTEC-9 study and highlight the potential of TECVAYLI to move a BCMA-directed bispecific antibody into earlier lines of therapy.
Yusri Elsayed, MD, M.H.Sc., PhD, Global Therapeutic Head of Oncology at Johnson & Johnson Innovative Medicine, stated that the MajesTEC-9 results further demonstrate TECVAYLI’s role as a first-in-class bispecific antibody and reflect the company’s commitment to delivering impactful therapies across all stages of multiple myeloma, with the long-term goal of improving outcomes and moving closer to a cure.
MajesTEC-9 Trial
MajesTEC-9 is a global(NCT05572515), randomized Phase 3 clinical trial evaluating TECVAYLI as a single-agent therapy compared with investigator’s choice of standard-of-care regimens in patients with relapsed or refractory multiple myeloma. The trial enrolled patients as early as first relapse, with the majority having disease refractory to both anti-CD38 monoclonal antibodies and lenalidomide, two commonly used frontline therapies.
Patients were randomized to receive TECVAYLI monotherapy or physician’s choice treatment, reflecting real-world clinical practice. The study was designed with progression-free survival as the primary endpoint and overall survival as a key secondary endpoint, aiming to determine whether a BCMA-targeted bispecific antibody could deliver superior outcomes earlier in the disease course.
Key Efficacy Findings
In the MajesTEC-9 study, TECVAYLI monotherapy demonstrated a 71% reduction in the risk of disease progression or death compared with standard-of-care regimens, including pomalidomide-based and carfilzomib-based combinations. Treatment with TECVAYLI was also associated with a 40% reduction in the risk of death, translating into a meaningful overall survival benefit.
These outcomes were achieved in a high-risk population with limited responsiveness to existing therapies, underscoring the clinical relevance of introducing an effective immunotherapy earlier in the treatment pathway.
Safety Profile
The safety profile of TECVAYLI in MajesTEC-9 was consistent with previously reported data, with no new safety signals identified. Adverse events were aligned with the known risk profile of bispecific T-cell engager therapies, including cytokine release syndrome and neurologic events, which are managed under established monitoring and treatment guidelines.
Mechanism of Action
TECVAYLI is a first-in-class bispecific T-cell engager antibody that simultaneously binds BCMA (B-cell maturation antigen) expressed on multiple myeloma cells and CD3 on T-cells. This dual targeting redirects the patient’s own T-cells to recognize and eliminate malignant plasma cells, enabling a targeted immune-mediated anti-tumor response.
Commenting on the results, Roberto Mina, MD, Associate Professor at the Winship Cancer Institute of Emory University, noted that the MajesTEC-9 findings reinforce the potential of TECVAYLI to move effective immunotherapy earlier in the multiple myeloma journey. He emphasized that TECVAYLI can be used broadly in community practice and delivers significant improvements in both progression-free and overall survival as a monotherapy, helping establish it as a key treatment option as early as first relapse.
TECVAYLI® is available only through a restricted program under the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS). The current indication is approved under the FDA’s accelerated approval pathway based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory clinical trials.
The MajesTEC-9 topline results are expected to be presented at upcoming scientific meetings and submitted to regulatory authorities to support potential updates to TECVAYLI’s labeling. If approved for earlier lines of therapy, TECVAYLI could represent a new standard of care for patients with relapsed multiple myeloma who have limited options following frontline treatment failure.
About Multiple Myeloma
Multiple myeloma is a malignant disorder of plasma cells and remains largely incurable despite advances in targeted therapies, immunomodulatory drugs, and monoclonal antibodies. Patients whose disease becomes refractory to anti-CD38 antibodies and lenalidomide face a poor prognosis, highlighting the need for more effective and durable treatment options in early relapse.
References
TECVAYLI® monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide, 14 January 2026, TECVAYLI® monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide
A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants with Relapsed or Refractory Multiple Myeloma (MajesTEC-9), ClinicalTrials.gov ID NCT05572515, https://clinicaltrials.gov/study/NCT05572515
MajesTEC-9: A randomized phase 3 study of teclistamab versus pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma, Meeting Abstract: 2023 ASCO Annual Meeting, J Clin Oncol 41, TPS8067(2023) Volume 41, Number 16_suppl DOI:10.1200/JCO.2023.41.16_suppl.TPS8067