Johnson & Johnson’s Phase 3 MonumenTAL-6 trial showed Tecvayli plus Talvey reduced disease progression or death by 89% and improved overall survival in relapsed or refractory multiple myeloma.
Written By: Meghana Jinka, PharmD
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson has reported positive topline results from the Phase 3 MonumenTAL-6 trial evaluating two investigational treatment regimens for adults with relapsed or refractory multiple myeloma (RRMM). Both Tecvayli (teclistamab-cqyv) plus Talvey (talquetamab-tgvs) and Talvey plus pomalidomide significantly improved progression-free survival (PFS) and overall survival (OS) compared with investigator’s choice of standard therapy in patients who had received one to four prior lines of treatment, including lenalidomide and an anti-CD38 antibody.
Dual Bispecific Strategy Targets Two Myeloma Antigens
Multiple myeloma is the second most common blood cancer worldwide and remains incurable despite substantial advances in treatment. Patients often relapse after successive therapies, highlighting the need for more effective options earlier in the treatment course.
Tecvayli is a BCMA-directed bispecific T-cell engager that redirects T cells to eliminate myeloma cells. Talvey targets GPRC5D, another protein highly expressed on myeloma cells. Combining these therapies enables simultaneous targeting of two distinct tumor antigens, a strategy intended to enhance anti-tumor activity while reducing the likelihood of treatment resistance.
Phase 3 MonumenTAL-6 Met Primary and Key Survival Endpoints
The global, randomized Phase 3 MonumenTAL-6 trial (NCT06208150) compared Tecvayli plus Talvey (Tec-Tal) and Talvey plus pomalidomide (Tal-P) against investigator’s choice of either elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd) in adults with relapsed or refractory multiple myeloma who had received one to four previous lines of therapy. The primary endpoint was progression-free survival assessed by an independent review committee. Key secondary endpoints included overall response rate, complete response or better, measurable residual disease-negative complete response, and overall survival.
Tecvayli plus Talvey produced the strongest results, reducing the risk of disease progression or death by 89% compared with standard therapy (HR 0.11; 95% CI, 0.08-0.16; p<0.0001). The combination also reduced the risk of death by 62% (HR 0.38), representing the lowest hazard ratio reported in a Phase 3 study evaluating bispecific therapies for relapsed or refractory multiple myeloma.
Talvey plus pomalidomide also met the primary endpoint, reducing the risk of disease progression or death by 73% (HR 0.27; 95% CI, 0.20-0.35) versus standard treatment. Safety findings for both investigational regimens remained consistent with the established safety profiles of the individual therapies, and no new safety signals were reported.
Based on the magnitude of benefit observed at the first interim analysis, the Independent Data Monitoring Committee recommended unblinding the study.
Experts Highlight Potential of Earlier Immunotherapy Combinations
Ajay K. Nooka, MD, MPH, Director of the Myeloma Program at Emory University School of Medicine, said the findings strengthen growing evidence supporting earlier use of immunotherapy combinations in multiple myeloma. He noted that simultaneous targeting of BCMA and GPRC5D produced deep and durable responses while offering an off-the-shelf treatment option suitable for broad clinical practice.
Yusri Elsayed, MD, Global Therapeutic Area Head of Oncology at Johnson & Johnson, said the results reinforce immunotherapy as a cornerstone of multiple myeloma treatment and support continued expansion of the company’s portfolio across different disease stages and therapeutic mechanisms.
Regulatory Path Forward
Johnson & Johnson plans to present the complete MonumenTAL-6 data at a future major medical meeting and submit the results to global health authorities. Positive findings from the trial could support regulatory filings to expand the use of Tecvayli- and Talvey-based combinations into earlier lines of therapy for patients with relapsed or refractory multiple myeloma. Both therapies are already approved in later-line settings, with Tecvayli recently gaining U.S. approval in combination with daratumumab for patients who have received at least one prior line of therapy.
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