• TALVEY^® plus daratumumab with or without pomalidomide showed progression-free survival of up to 81.3% and overall survival of up to 89.2% at 24 months¹
  
  
• MonumenTAL-3 is the third positive study in recent months from Johnson & Johnson’s bispecific portfolio and is the first Phase 3 study of a GPRC5D bispecific investigational combination^1,2,3
  
  
• Results reinforce Johnson & Johnson’s leadership in multiple myeloma, advancing bispecific combinations earlier in the treatment journey, and expanding options to match the right treatment to the right patient and stage of disease¹

Johnson & Johnson announced results from the investigational Phase 3 MonumenTAL-3 study.¹ The results showed that TALVEY^®(talquetamab), a GPRC5D bispecific antibody, in combination with daratumumab with or without pomalidomide demonstrated significant reduction in the risk of disease progression or death of up to 72.0%, and clinically meaningful reduction of up to 53.0% in the risk of death, compared to the standard regimen of daratumumab, pomalidomide, and dexamethasone (DPd) in patients with relapsed or refractory multiple myeloma (RRMM).¹ Results showed a progression-free survival (PFS) rate of up to 81.3% versus standard of care (51.2%) and an overall survival (OS) rate of up to 89.2% versus standard of care (79.1%) at 24 months.¹  

This is the first Phase 3 study to demonstrate superior PFS with a GPRC5D bispecific antibody combination in earlier-line multiple myeloma, underscoring the potential of this regimen to advance bispecific combinations earlier in the treatment paradigm.¹ Results were presented at the 2026 European Hematology Association (EHA) Annual Meeting (Abstract #S100), with simultaneous publication in The New England Journal of Medicine.^1,4

Expert and company perspectives support bispecific combinations in earlier lines
“The impressive results from this study point to the promise of talquetamab plus daratumumab as a potential new bispecific combination for patients with relapsed or refractory multiple myeloma,” said Peter Voorhees, M.D., Professor of Hematology and Oncology at Atrium Health, Levine Cancer Institute at Wake Forest University School of Medicine.* “Talquetamab works with daratumumab in earlier lines—a critical time for treating patients with the most effective regimens.”

“Daratumumab-based regimens have transformed the treatment of multiple myeloma and remain a foundational therapy across all stages of disease. The MonumenTAL-3 study builds on this legacy, combining daratumumab with talquetamab, the first GPRC5D bispecific antibody, to further expand the effective options available to patients in the relapsed/refractory setting,” said Ester in  ‘t Groen, EMEA Therapeutic Area Head, Haematology, Johnson & Johnson. “These findings reflect Johnson & Johnson’s commitment to leveraging the power of our portfolio to advance novel combination regimens that address the evolving and highly heterogeneous needs of patients living with multiple myeloma.”

“The MonumenTAL-3 findings underscore our commitment to bringing bispecific combinations into earlier lines of therapy, building on the strength and breadth of Johnson & Johnson’s multiple myeloma portfolio,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Head, Oncology, Johnson & Johnson. “These results add to our growing body of evidence across bispecific antibodies and reinforce our strategy of advancing differentiated immunotherapies to better match the right therapy to the right patient at each stage of disease.”

Novel mechanism spares healthy immune cells
Talquetamab targets a protein called GPRC5D, which is found on multiple myeloma cells (as well as some healthy cells in the body).¹ GPRC5D expression is independent of other targets, including BCMA, and is absent or expressed at low levels on normal B-Cells.¹ Talquetamab works by targeting myeloma cells while largely sparing healthy B-cells.¹ With daratumumab priming the immune system for enhanced talquetamab activity, the combination benefits from complementary mechanisms of action, supporting the potential effectiveness of this approach in multiple myeloma.^1,5,6

Phase 3 MonumenTAL-3 study results
The MonumenTAL-3 study evaluated talquetamab with daratumumab subcutaneous (SC) or talquetamab with daratumumab SC (Tal-D) and pomalidomide (Tal-DP) compared to DPd in patients with RRMM who have received at least one prior line of therapy.¹ At a median follow-up of two years (24.6 months), results showed significant improvement in PFS for Tal-DP (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.20-0.40; p<0.0001) and Tal-D (HR, 0.33; 95% CI, 0.24-0.46; p<0.0001).¹ At 24 months, Tal-DP showed a PFS rate of 81.3% and Tal-D showed a PFS rate of 77.6%.¹ All participants (N=864) were previously exposed to lenalidomide and a proteasome inhibitor and received at least one prior line of therapy.¹ Most patients enrolled were refractory to lenalidomide (85.1%) and their last line of therapy (93.4%), and some were exposed to an anti-CD38 antibody (11.8%).⁴

Statistically significant improvements compared to DPd were observed across key secondary endpoints of overall response rate (ORR), complete response or better (≥CR), and minimal residual disease (MRD)-negative ≥CR (10^-5, next-generation sequencing [NGS]) for Tal-DP and Tal-D.¹ ORRs (88.2%, 88.5%, 77.6%), ≥CR rates (71.1%, 68.9%, 34.5%) and MRD-negative ≥CR rates (52.3%, 46.3%, 15.9%) were significantly higher for Tal-DP and Tal-D vs DPd, respectively, after two years median follow-up.¹ Clinically meaningful improvement in OS was shown with Tal-DP (HR, 0.47; 95% CI, 0.30-0.73, p=0.0006) and Tal-D (HR, 0.51; 95% CI, 0.33-0.78, p=0.0015) vs DPd.¹ At 24 months, Tal-DP delivered an OS rate of 89.2% and Tal-D delivered an OS rate of 87.9%.¹

The overall safety profiles for the talquetamab plus daratumumab SC treatment arms were consistent with the known safety profiles of each monotherapy, and a reduced risk of severe infections were observed in the Tal-D arm compared to the standard of care.¹ Overall, rates of Grade 3/4 treatment-emergent adverse events (TEAEs) were comparable across treatment arms (94.9% with Tal‑DP, 74.8% with Tal‑D, and 91.5% with DPd).⁴ Infections occurred at rates of 87.3% (Tal‑DP), 84.3% (Tal‑D), and 83.0% (DPd).¹ When analysing severe infections, Tal-D had the lowest rate of Grade 3/4 infections (29.2%), followed by Tal-DP (37.7%), and DPd (42.2%).¹ There were some instances of Grade 5 adverse events (AEs) across the entire population of the study; the Tal-DP arm saw the fewest (1.8%), followed by Tal-D (4.0%) and DPd (4.6%), with approximately 0.7% (Tal-DP), 1.5% (Tal-D), and 1.8% (DPd) due to infections.⁴ Treatment discontinuations due to AEs occurred in 10.5% of Tal‑DP, 8.0% of Tal‑D, and 6.7% of DPd patients.¹ At data cutoff, 70.3% (Tal-DP), 69.7% (Tal-D), and 47.3% (DPd) of patients remained on study treatment.¹ Cytokine release syndrome occurred in 67.8% (Tal‑DP) and 58.4% (Tal‑D) of patients and was predominantly Grade 1–2, while immune effector cell‑associated neurotoxicity syndrome was infrequent (2.9% and 1.8% respectively), with no Grade ≥4 events reported.¹ Across Tal-DP, Tal-D and DPd, respectively, taste change (72.8%, 74.8%, 3.9%) and weight loss (45.7%, 38.3%, 7.4%) AEs along with ataxia/balance disorders (Grade 1-2: 11.6%, 10.2%, 0.4%; Grade 3: 2.9%, 2.2%, 0.0%) were primarily low grade and rarely led to talquetamab discontinuation, supporting the manageable safety profile.^1,4

Based on these results, Johnson & Johnson is working with regulatory bodies globally to bring the benefits of talquetamab plus daratumumab SC with or without pomalidomide to eligible patients as quickly as possible. On 31 March 2026, the Company submitted a type II variation to the European Medicines Agency (EMA) for the use of talquetamab in combination with daratumumab, or in combination with daratumumab and pomalidomide, for the treatment of adult patients with RRMM who have received at least one prior therapy.