The FDA has awarded a national priority voucher to teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex) for patients with relapsed/refractory multiple myeloma.1
The Commissioner’s National Priority Voucher (CNPV) is intended to accelerate the review of products with the potential to aid in at least 1 national health priority in the United States (US), such as addressing a public health crisis; delivering more innovative cures for the American people; addressing a large unmet medical need; promoting domestic drug development and manufacturing to advance the health interests of Americans and strengthen US supply chain resiliency; and increasing affordability. Teclistamab plus daratumumab is the 16th product/regimen to receive a national priority voucher through the CNPV program.
Under the CNPV program, review decisions for designated products/combinations are targeted for 1 to 2 months following the submission of an application. This allows for an expedited review period compared with the 6 months used for FDA priority reviews and 10 months for standard reviews.2
The voucher for teclistamab plus daratumumab was supported by data from the phase 3 MajesTEC-3 trial (NCT05083169), which were presented at the 2025 ASH Annual Meeting and Exposition.1 Findings showed that at a median follow-up of 34.5 months for patients with relapsed/refractory multiple who received 1 to 3 prior lines of therapy, those treated with teclistamab plus daratumumab (n = 291) achieved a median progression-free survival (PFS) that was not reached (NR) compared with 18.1 months for those given daratumumab plus pomalidomide (Pomalyst) and dexamethasone (DPd) or daratumumab plus bortezomib (Velcade) and dexamethasone (DVd; n = 296; HR, 0.17; 95% CI, 0.12-0.23; P < .0001).3 The 36-month PFS rates were 83.4% for teclistamab/daratumumab vs 29.7% for DPd or DVd.
How was the MajesTEC-3 trial designed?
Investigators enrolled patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy that included a proteasome inhibitor and lenalidomide (Revlimid). Patients who received only 1 prior line of therapy needed to be refractory to lenalidomide per International Myeloma Working Group criteria. An ECOG performance status of 0 to 2 was required for all patients, and patients were excluded if they received prior BCMA-directed therapy or were refractory to anti-CD38 monoclonal antibodies.
Patients were randomly assigned 1:1 to receive teclistamab plus daratumumab or investigator’s choice of DPd or DVd; notably, 91% of patients in the control arm received DPd. In the experimental arm, teclistamab was given via step-up dosing at 1.5 mg/kg on days 2, 4, 8, 15, and 22 of cycle 1, then days 1, 8, 15, and 22 of cycle 2. The full dose of 3 mg/kg was started in cycle 3 and was given on days 1 and 15 of cycles 3 to 6, then once every 4 weeks in cycles 7 and beyond. Subcutaneous daratumumab was given at 1800 mg on days 1, 8, 15, and 22 of cycles 1 and 2, once every 2 weeks in cycles 3 to 6, and once every 4 weeks in cycle 7 and beyond. In the experimental arm, dexamethasone was also administered as premedication on days 1, 2, 4, and 8 of cycle 1.
PFS per independent review committee assessment served as the trial’s primary end point. Secondary end points included complete response (CR) or better rate and overall response rate (ORR); minimal residual disease (MRD)–negativity rate, overall survival (OS), symptom score, safety, and pharmacokinetics/immunogenicity.
What additional data were reported from MajesTEC-3?
Results also showed that patients in the teclistamab plus daratumumab arm achieved an ORR of 89.0% compared with 75.3% for DPd or DVd (odds ratio [OR], 2.65; 95% CI, 1.68-4.18; P <.0001). The CR or better rates were 81.8% and 32.1%, respectively (OR, 9.56; 95% CI, 6.47-14.14; P < .0001).
MRD negativity at a 10-5 sensitivity was reported in 58.4% of evaluable patients in the teclistamab plus daratumumab arm (n = 262) compared with 17.1% of patients in the DPd/DVd arm (n = 269; OR, 6.78; P < .0001).
The median OS was NR in both arms, although a significant improvement was observed in the teclistamab plus daratumumab group (HR, 0.46; 95% CI, 0.32-0.65; P < .0001). The 36-month OS rates were 83.3% for teclistamab plus daratumumab vs 65.0% for DPd/DVd.
Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 100% of patients in both arms. Grade 3/4 TEAEs were reported in 95.1% of patients in the experimental arm vs 96.6% of patients in the control arm. TEAEs led to treatment discontinuation in 4.6% of patients in the teclistamab plus daratumumab arm vs 5.5% of patients in the DPd/DVd arm. Serious AEs were reported in 70.7% and 62.4% of patients, respectively. TEAEs led to deaths in 7.1% of patients in the teclistamab plus daratumumab group vs 5.9% of patients in the DPd/DVd group.
The most common any-grade hematologic TEAEs included neutropenia (teclistamab/daratumumab arm, 78.4%; DPd/DVd arm, 82.8%), anemia (39.2%; 35.5%), thrombocytopenia (36.4%; 43.4%), lymphopenia (22.3%; 17.2%), and leukopenia (18.0%; 21.0%). The most common non-hematologic TEAEs comprised cytokine release syndrome (CRS; 60.1%; 0%), diarrhea (51.9%; 30.7%), cough (48.1%; 22.8%), and pyrexia (36.7%; 19.0%).
In the experimental arm, CRS occurred primarily at grade 1, occurring in 44.2% of patients. Grade 2 CRS was reported in 15.9% of patients, and no grade 3 or higher CRS occurred. All CRS events resolved, and no grade 2 or higher instances were reported after the first cycle. Notably, no prophylactic tocilizumab (Actemra) was given, per trial protocol.
References
- FDA proactively awards national priority voucher based on strong phase 3 study results. FDA. December 15, 2025. Accessed December 15, 2025. https://www.fda.gov/news-events/press-announcements/fda-proactively-awards-national-priority-voucher-based-strong-phase-3-study-results
- Priority review. FDA. January 4, 2018. Accessed December 15, 2025. https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review
- Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of MajesTEC-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6
