MonumenTAL-6 Phase 3 Trial: Tecvayli + Talvey Combination Cuts Risk of Progression or Death by 89% in Relapsed/Refractory Multiple Myeloma

Trial Design

MonumenTAL-6 is the first Phase 3 trial to evaluate the combination of two bispecific antibodies — Tecvayli (targeting BCMA) and Talvey (targeting GPRC5D) — against standard care .

• Type: Multicenter, randomized, open-label, Phase 3 study .
• Two experimental arms: Talquetamab plus pomalidomide (Tal-P) and talquetamab plus teclistamab (Tal-Tec) .
• Control arm: Investigator's choice of elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd) .
• Patient population: RRMM with 1–4 prior lines of therapy, all previously treated with lenalidomide and an anti-CD38 monoclonal antibody .
• Primary endpoint: Progression-free survival (PFS) per IMWG criteria. Secondary endpoints include overall survival (OS), overall response rate (ORR), and safety .

Key Efficacy Results

The topline press release reported the following risk reductions for the Tal-Tec combination versus standard of care :

• Risk reduction for progression or death: 89%. This corresponds to a hazard ratio of approximately 0.11, though the exact HR and confidence intervals were not disclosed in the topline release .
• Risk reduction for death: 62%, corresponding to an approximate HR of 0.38 .
• Both PFS and OS endpoints were met with statistical significance for both investigational arms versus the control arm .

Safety Profile

The press release confirms that the safety profile of the combination was consistent with the known safety profiles of the individual agents (teclistamab and talquetamab), which include cytokine release syndrome (CRS), infections, cytopenias, and GPRC5D-related skin/nail/taste adverse events . No new safety signals were identified in the trial . The detailed safety data will be presented at the upcoming medical meeting.

Broader Context: J&J's Positive Phase 3 Results in Earlier-Line Myeloma

MonumenTAL-6 is one of several recent positive Phase 3 trials from J&J that position their bispecific antibodies for earlier use in the myeloma treatment pathway:

• MajesTEC-9 (teclistamab, first relapse): Tecvayli as a single agent demonstrated superior PFS and OS versus standard combinations (PVd or Kd) in patients at first relapse, with an 18-month PFS of 69.8% vs. 26.9% (HR ~0.29) . These results support moving Tecvayli into earlier lines of therapy .
• MajesTEC-7 (teclistamab + daratumumab): The combination of Tecvayli plus daratumumab achieved a 36-month PFS of 83.4% vs. 29.7% (HR=0.17) in earlier-line RRMM, and a CHMP recommendation was issued in June 2026 for this regimen as a potential new standard of care .
• MonumenTAL-3 (talquetamab + daratumumab): Talvey in combination with daratumumab and/or pomalidomide showed PFS hazard ratios of 0.28 and 0.33 versus standard of care .

MonumenTAL-6 is the first Phase 3 trial to evaluate the combination of two bispecific antibodies (anti-BCMA and anti-GPRC5D) against standard care, and its strongly positive results reinforce J&J's strategy of using bispecific-based regimens across multiple lines of therapy in multiple myeloma .

Caveat

These are topline results from a company press release; peer-reviewed publication and full data presentation are needed for independent verification of the exact hazard ratios, confidence intervals, and detailed safety data.