Positive topline results from the randomized three-arm Phase 3 MonumenTAL-6 trial announced: Tec-Tal and Tal-P investigational arms showed improved PFS and OS vs standard of care (EPd or PVd) control arm in RRMM
On Thursday, July 23, Johnson & Johnson announced positive topline results from the randomized three-arm Phase 3 MonumenTAL-6 trial, evaluating Tecvayli® (teclistamab-cqyv) plus Talvey® (talquetamab-tgvs) and Talvey plus pomalidomide in adults with relapsed or refractory multiple myeloma (RRMM) who had received one to four prior lines of therapy, including an anti-CD38 antibody and lenalidomide. The two investigational arms were compared to investigator’s choice of standard of care as the third arm: elotuzumab, pomalidomide and dexamethasone (EPd); or pomalidomide, bortezomib and dexamethasone (PVd).
In a press release, Johnson & Johnson said that the randomized, three-arm study met its primary endpoint of progression-free survival (PFS) for both investigational treatment arms (Tec-Tal, Tal-P) compared with investigator's choice of standard of care (EPd or PVd).
Topline results showed that the Tec-Tal combination reduced the risk of disease progression or death by 89% versus standard of care (hazard ratio [HR] 0.11; 95% confidence interval [CI] 0.08–0.16; p<0.0001). The combination also reduced the risk of death by 62% (HR 0.38).
The Tal-P regimen reduced the risk of disease progression or death by 73% (HR 0.27; 95% CI 0.20–0.35). Both investigational regimens demonstrated statistically significant improvements in overall survival compared with standard treatment. The company disclosed the overall survival hazard ratio only for the Tec-Tal arm.
The company stated that the hazard ratio of 0.11 observed with Tec-Tal is the lowest reported in a Phase 3 study evaluating bispecific therapies in RRMM.
The study evaluated a dual-antigen approach targeting B-cell maturation antigen (BCMA) with teclistamab and G protein-coupled receptor class C group 5 member D (GPRC5D) with talquetamab. MonumenTAL-6 is the first Phase 3 trial to evaluate a regimen targeting both BCMA and GPRC5D in RRMM.
Overall safety profiles of the Tec-Tal and Tal-P treatment arms were consistent with the known safety profiles of each monotherapy.
Based on the interim analysis, the Independent Data Monitoring Committee (IDMC) recommended that the study be unblinded. Full study results will be presented at a future medical meeting and submitted to global health authorities.
The MonumenTAL-6 Study
MonumenTAL-6 (NCT06208150) is a global, randomized Phase 3 trial comparing Tec-Tal, and Tal-P with investigator's choice of EPd or PVd in patients with RRMM who had received one to four prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.
The primary endpoint is independently assessed progression-free survival. Key secondary endpoints include overall response rate, complete response or better, minimal residual disease-negative complete response, and overall survival.
Current approved indications in the U.S. for Tecvayli and Talvey
In the U.S., Tecvayli (teclistamab-cqyv) is approved:
• In combination with daratumumab and hyaluronidase-fihj for adults with RRMM who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
• As monotherapy for adults with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
Talvey (talquetamab-tgvs) is approved for adults with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. The indication is under accelerated approval based on response rate and durability of response, with continued approval contingent on confirmatory clinical benefit.
Safety information from U.S. Prescribing Information
The following safety information reflects the current U.S. Prescribing Information for Tecvayli and Talvey and is not specific to the MonumenTAL-6 trial results.
Tecvayli (teclistamab-cqyv)
Tecvayli carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).
The drug is available only through the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS) program.
Other important warnings and precautions for Tecvayli include hepatotoxicity, severe or fatal infections, neutropenia, hypersensitivity and administration-related reactions, and embryo-fetal toxicity. Patients should be monitored for CRS, neurologic toxicity, liver function abnormalities, infections, hematologic toxicities and injection-related reactions. Driving or operating hazardous machinery is not recommended during the step-up dosing period and for 48 hours afterward, or until neurologic symptoms resolve if they occur.
The most common adverse reactions reported with Tecvayli monotherapy (≥20%) include pyrexia, CRS, musculoskeletal pain, injection-site reactions, fatigue, upper respiratory tract infection, nausea, headache, pneumonia and diarrhea. When used with daratumumab and hyaluronidase-fihj, the most common adverse reactions include hypogammaglobulinemia, upper respiratory tract infection, CRS, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection-site reactions, fatigue, pyrexia, headache, nausea, gastroenteritis and weight loss. Common Grade 3–4 laboratory abnormalities include decreased lymphocytes, neutrophils, white blood cells, hemoglobin and platelets.
Please read the full prescribing information (including boxed warning) for Tecvayli.
Talvey (talquetamab-tgvs)
Talvey (talquetamab-tgvs) carries a boxed warning for CRS and neurologic toxicity, including ICANS, and is available only through the shared Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS) program.
Additional important warnings for Talvey include oral toxicity and weight loss, infections, cytopenias, skin toxicity, hepatotoxicity and embryo-fetal toxicity. Patients should be monitored for CRS, neurologic toxicity, oral symptoms, weight loss, infections, blood count abnormalities, skin reactions and liver function changes. Patients are advised not to drive or operate hazardous machinery during the step-up dosing period, for 48 hours afterward, or until neurologic symptoms resolve if they develop.
The most common adverse reactions reported with Talvey (≥20%) include pyrexia, CRS, dysgeusia, nail disorders, musculoskeletal pain, skin disorders, rash, fatigue, weight loss, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension and headache. The most common Grade 3–4 laboratory abnormalities include decreased lymphocyte count, neutrophil count, white blood cell count, and hemoglobin.
Please read the full prescribing information (including boxed warning) for Talvey.
References:
TECVAYLI® + TALVEY® reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. Johnson & Johnson press release. July 23, 2026.
Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS) program.
Tecvayli Full Prescribing Information. Johnson & Johnson.
Talvey Full Prescribing Information. Johnson & Johnson.