Phase 3 MajesTEC-3 Study Delivers Unprecedented Results, Positioning TECVAYLI® Plus DARZALEX FASPRO® as a Potential New Standard of Care as Early as Second-Line Treatment for Relapsed/Refractory Multiple Myeloma
Johnson & Johnson, the worldwide leader in multiple myeloma, today announced new data from the investigational Phase 3 MajesTEC-3 study that demonstrate the potential of TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® as early as second line for patients with relapsed/refractory multiple myeloma (RRMM). Results show an 83% reduction in the risk of disease progression or death compared to standard regimens at nearly three-years follow-up (hazard ratio [HR], 0.17; 95 percent confidence interval [CI], 0.12-0.23; P<0.0001).1 Ninety-one percent of patients who were progression-free at six months remained progression-free at three years.2
The study evaluated the efficacy and safety of the investigational immunotherapy combination of TECVAYLI® plus DARZALEX FASPRO® versus DARZALEX FASPRO® and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with RRMM who have received 1-3 prior lines of therapy. The data were presented as a late-breaking oral presentation and in the press program at the 2025 American Society of Hematology (ASH) Annual Meeting, with simultaneous publication in The New England Journal of Medicine.
“The combination of TECVAYLI and DARZALEX FASPRO offers remarkable efficacy, a well-characterized safety profile with robust infection management protocols, and an opportunity to improve patient outcomes across academic and community settings. It has the potential to change the standard of care as a steroid-sparing combination regimen suited for outpatient administration on the familiar DARZALEX schedule,” said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Hematology, University Hospital of Salamanca.* “TECVAYLI and DARZALEX FASPRO work synergistically by uniquely targeting both BCMA and CD38 to prime and activate the immune system. The combination has shown to extend progression-free survival and overall survival versus standard of care as early as second line.”
Significant improvements compared to standard of care were observed across key secondary endpoints, including treatment response rates, minimal residual disease (MRD)-negativity, overall survival (OS), and time to worsening of symptoms – revealing the comprehensive impact of the combination across varied patient measures.1 TECVAYLI® plus DARZALEX FASPRO®showed higher rates of complete response (≥CR) (81.8% vs. 32.1%; odds ratio [OR], 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs. 75.3%; OR, 2.65; 95% CI, 1.68-4.18) and MRD-negativity (58.4% vs. 17.1%; OR, 6.78; 95% CI, 4.53-10.15, P<0.0001; evaluable rate of 89.3% vs. 63.0%) at three-years follow-up.1
OS favored TECVAYLI® plus DARZALEX FASPRO® (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001) across all prespecified subgroups. At three-years, OS rates were 83.3% and 65.0%, respectively.1 Additionally, patients remained symptom-free significantly longer with TECVAYLI® plus DARZALEX FASPRO® versus standard of care, underscoring a significant improvement in patient-reported quality of life (QoL) outcomes.1
With these data, we are entering a new era in treating multiple myeloma with the first bispecific combination to demonstrate superior overall survival as early as second line. Alongside the other transformational therapies in our leading portfolio, we can offer patients optimal outcomes at any stage of disease – bringing us closer to our ultimate ambition to find a cure,” said Sen Zhuang, M.D., Vice President, Oncology Clinical Research, Johnson & Johnson Innovative Medicine. “With TECVAYLI plus DARZALEX FASPRO we have the potential to set a new standard of care once again for this disease. We continue to explore how regimens with our bispecifics portfolio can redefine the future for patients.”
In the study, TECVAYLI® plus DARZALEX FASPRO® and standard of care comparators had similar rates of Grade 3/4 (95.1% vs. 96.6%) treatment-emergent adverse events (TEAE).1 Most Grade 3/4 events were due to cytopenia and infection.1 Infections were observed with TECVAYLI® and DARZALEX FASPRO®(any grade, 96.5%; Grade 3/4, 54.1%) and DPd/DVd control (any grade 84.1%; Grade 3/4 43.4%). Grade 3 or higher infections with TECVAYLI® and DARZALEX FASPRO® declined after the first 6 months of treatment with use of established immunoglobulin supplementation and infection prophylaxis protocols, along with switch to monthly dosing.1
Cytokine release syndrome occurred in 60.1% of patients; all cases were Grade 1/2, did not lead to treatment discontinuation and were effectively managed using standard guidelines.1 Immune effector cell-associated neurotoxicity syndrome was rare and occurred in 1.1% of patients.1 Serious adverse events occurred in 70.7% of patients compared to 62.4% of patients treated with the control regimen, while treatment discontinuations due to adverse events were low (4.6% vs. 5.5%).1 Grade 5 TEAEs were 7.1% and 5.9% with TECVAYLI® plus DARZALEX FASPRO®and DPd/DVd control, respectively.1
Based on these results, Johnson & Johnson is working with regulatory bodies globally to bring the benefits of this bispecific regimen to eligible patients as quickly as possible. The Company has submitted a supplemental Biologics License Application (sBLA) for the use of TECVAYLI® and DARZALEX FASPRO® in combination as a treatment for RRMM to the U.S. Food and Drug Administration (FDA). The FDA has granted Breakthrough Therapy Designation (BTD) for the combination regimen; BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).
The sBLA is being reviewed through the Real-Time Oncology Review (RTOR) program, which enables the agency to initiate their evaluation of the data before the full application is formally submitted. An application has also been submitted to Brazil’s health agency, ANVISA (Agência Nacional de Vigilância Sanitária).
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