Phase 3 MajesTEC-9 Trial Shows Survival Benefit With Teclistamab in Multiple Myeloma

Topline results from a new drug trial show that teclistamab-cqyv (Tecvayli; Janssen Biotech) monotherapy offers significant survival benefits for patients with multiple myeloma (MM).

In the phase 3 randomized MajesTEC-9 study (NCT05572515), teclistamab-cqyv showed a 71% reduction in the risk of disease progression or death and a 40% reduction in the risk of death in patients who were largely refractory to anti-CD38 therapy and lenalidomide (Revlimid; Celgene).^1,2

“[Teclistamab-cqyv] continues to break new ground as a first-in-class bispecific T-cell engager antibody, and the MajesTEC-9 results are the latest example of Johnson & Johnson’s commitment to provide critical treatment options for patients at every stage of their disease,” Yusri Elsayed, MD, MHSc, PhD, global therapeutic head of oncology at Johnson & Johnson Innovative Medicine, said in a news release.

The MajesTEC-9 study evaluated teclistamab monotherapy in patients who were predominantly refractory to anti-CD38 and lenalidomide therapies. These findings build on the MajesTEC-3 results (NCT05083169), which was a phase 3 randomized study that compared the efficacy of teclistamab daratumumab with daratumumab (Darzalex Faspro; Janssen Biotech) subcutaneously (SC) in combination with pomalidomide (Pomalyst; Celgene) and dexamethasone (DPd, Decadron; Merck) or daratumumab SC in combination with bortezomib (Velcade; Millennium Pharmaceuticals) and dexamethasone (DVd). The results, which were published in The New England Journal of Medicine, demonstrated significant improvements in progression-free and overall survival with teclistamab combined with daratumumab SC in patients who were naïve or sensitive to anti-CD38 therapy.^3,4

Understanding the Phase 3 MajesTEC-9 Trial

The current phase 3 MajesTEC-9 study evaluates the efficacy and safety of teclistamab-cqyv, a bispecific T-cell engager antibody, compared with standard-of-care regimens in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy. All enrolled patients had previously been treated with anti-CD38 monoclonal antibody and lenalidomide. Most patients were refractory to anti-CD38 therapy and lenalidomide, and over 90% were refractory to their most recent line of treatment.¹

Patients randomized to teclistamab-cqyv displayed a clinically meaningful and statistically significant 71% reduction in the risk of disease progression or death. Further results demonstrated that teclistamab reduced the risk of death by 40% compared with control treatment. However, full study results will be presented at an upcoming medical meeting.¹

“The MajesTEC-9 results reinforce the potential of [teclistamab-cqyv] to transform treatment earlier in the MM journey, with an immunotherapy regimen widely available for all appropriate patients, including those commonly treated in the community setting,” Roberto Mina, MD, associate professor at Winship Cancer Institute of Emory University and formerly assistant professor at the University of Turin in Turin, Italy, said in a news release.¹

The safety profile in the study was consistent with its known profile, with no new safety concerns. In the previous MajesTEC-3 study, the safety profile of teclistamab in combination with daratumumab SC was comparable to the standard of care, with grade 3.4 events mainly due to cytopenias and infections.^1,4

“The impressive results show a significant improvement in progression-free and overall survival as a monotherapy in patients with refractory multiple myeloma and, together with the MajesTEC-3 results, help establish [teclistamab-cqyv] as an essential therapy for patients as early as first relapse,” Mina said in the news release.¹

How Does Teclistamab Fit Into the MM Therapeutic Landscape?

As a first-in-class, bispecific T-cell engager antibody therapy, teclistamab activates the immune system by binding to the CD3 receptor on T cells and the B-cell maturation antigen (BCMA) antigen on MM cells. This therapy offers new treatment options for MM, which is known to have high rates of relapse.¹

Teclistamab received FDA accelerated approval in October 2022 as a ready-to-use antibody SC treatment for patients with relapsed or refractory MM who received at least 4 lines of prior therapy. The FDA also approved a supplemental biologics license application for teclistamab in February 2024, which allowed reduced dosing frequency of 1.5 mg/kg every 2 weeks for patients with relapsed or refractory MM who have maintained a complete response for at least 6 months.¹

REFERENCES

1. TECVAYLI^® monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as the first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. News release. Johnson & Johnson. January 14, 2026. Accessed January 15, 2026. https://www.jnj.com/media-center/press-releases/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

2. A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-9). Updated December 19, 2025. Accessed January 15, 2026. https://clinicaltrials.gov/study/NCT05572515

3. A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-3). Updated December 19, 2025. Accessed January 15, 2026. https://clinicaltrials.gov/study/NCT05083169

4. Unprecedented results from the Phase 3 MajesTEC-3 study support TECVAYLI^® plus DARZALEX FASPRO^® as a potential standard of care as early as second line for patients with relapsed/refractory multiple myeloma. News release. Johnson & Johnson. December 9, 2025. Accessed January 15, 2026. https://www.jnj.com/media-center/press-releases/unprecedented-results-from-the-phase-3-majestec-3-study-support-tecvayli-plus-darzalex-faspro-as-a-potential-standard-of-care-as-early-as-second-line-for-patients-with-relapsed-refractory-multiple-myeloma