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TECVAYLI®

(teclistamab-cqyv)

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TECVAYLI® (teclistamab-cqyv)

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TECVAYLI - MajesTEC-3 Study

Last Updated: 12/09/2025

SUMMARY  

  • Johnson & Johnson does not recommend the use of TECVAYLI or DARZALEX FASPRO® (daratumumab and hyaluronidase) in a manner inconsistent with the approved labeling.
  • MajesTEC-3 is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO (Tec-Dara subcutaneous [SC]) vs investigator’s choice of DARZALEX FASPRO, pomalidomide, and dexamethasone (DPd) or DARZALEX FASPRO, bortezomib, and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines of therapy (LOT).1
    • Costa et al (2025)1 reported initial efficacy and safety results of the MajesTEC-3 study at a median follow-up of 34.5 months.
      • The estimated 36-month progression free survival (PFS) was 83.4% vs 29.7% (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12-0.23; P<0.0001) for Tec-Dara SC vs DPd/DVd, respectively.
      • Serious adverse events (AEs) occurred in 70.7% vs 62.4% of patients in the TEC-DARA SC arm vs DPd/DVd arm, and deaths due to treatment-emergent adverse events (TEAEs) was reported in 7.1% vs 5.9%, respectively.

PRODUCT LABELING

CLINICAL DATA - MAJESTEC-3 STUDY

MajesTEC-3 (NCT05083169) is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO vs DPd or DVd (investigator’s choice) in patients with RRMM after 1-3 prior LOT.1

Study Design/Methods

  • The study design is presented in Figure: MajesTEC-3 Study Design.1
  • Pateints were randomized between October 22, 2021 and September 29, 2023 across 20 countries at 150 sites.1 
  • Infection prophylaxis was administered according to the guidelines set by the institution and included the following: immunoglobulin supplementation, antibiotics, Pneumocystis jirovecii pneumonia prophylaxis, and herpes zoster reactivation. In a February 2023 protocol amendment, immunoglobulin replacement therapy and infection prophylaxis guidance was reinforced. This underscores the importance of immunoglobulin G level monitoring and compliance with protocol guidance on immunoglobulin supplementation. The administration of tocilizumab was permitted for grade 1 CRS and recommended for grade ≥2.1

MajesTEC-3 Study Design1,2

Abbreviations: BCMA, B-cell maturation antigen; CR, complete response; DPd, daratumumab + pomalidomide + dexamethasone; DVd, daratumumab + bortezomib + dexamethasone; Dara, daratumumab; ECOG PS, Eastern Cooperative Oncology Group performance status; HRQoL, health-related quality of life; IRC, independent review committee; ISS, International Staging System; IV, intravenous; LOT, line of therapy; mAb, monoclonal antibody; MRD, minimal residual disease; MySIm-Q TTS, Multiple Myeloma Symptom and Impact Questionnaire Total Symptom Score; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor; PO, by mouth; Q4W, every 4 weeks; Q2W, every 2 weeks; QW, weekly; R, randomization; RRMM, relapsed/refractory multiple myeloma; SC, subcutaneous; SUD, step-up dose; Tec, teclistamab.
aRandomization was stratified by choice of DPd or DVd, ISS disease stage, previous anti-CD38 exposure, and the number of prior LOTs.
bPrior exposure to anti-CD38 mAbs was permitted.
cDexamethasone, acetaminophen, and diphenhydramine premedication was required for the first 2 weeks; subsequent dexamethasone was not required thereafter.
dInvestigator’s choice of DPd/DVd treatment per established schedules.
eResponse and disease progression were assessed by a blinded IRC per IMWG criteria.
fTwo SUDs of 0.6 and 0.3 mg/kg were administered on days 2 and 4, respectively, followed by the first treatment dose of 1.5 mg/kg on day 8 and 1.5 mg/kg weekly thereafter.

Costa et al (2025)1 reported initial efficacy and safety results of the MajesTEC-3 study at a median follow-up of 34.5 months.

Results

Treatment Disposition and Baseline Characteristics

  • Of the 587 patients randomized (Tec-Dara SC, n=291; DPd/DVd, n=296), 573 patients (Tec-Dara SC, n=283; DPd/DVd, n=290) received study treatment.1 
    • Of the 290 patients who received DPd/DVd, 90.7% (n=263) received DPd and 9.3% (n=27) received DVd.
  • The baseline demographics and disease characteristics were comparable between the Tec-Dara SC and DPd/DVd treatment arms.1,2 
    • The median age was 64 years (range, 36-88) in the Tec-Dara SC arm, with 10.7% (n=31) of patients ≥75 years and 63 years (range, 25-84) in the DPd/DVd arm, with 8.4% (n=25) of patients ≥75 years.
    • In the Tec-Dara SC arm, 8.2% (n=24) of patients were classified as International Staging System (ISS) disease stage III compared to 7.8% (n=23) in the DPd/DVd arm.
    • The presence of soft-tissue plasmacytomas was observed in 14.1% (n=41) of patients in the Tec-Dara SC arm and 13.9% (n=41) of patients in the DPd/DVd arm.
    • The presence of high-risk cytogenetics (≥1 of del[17p], t[4;14], or t[14;16]) was observed in 36.5% (n=104/285) of patients in the Tec-Dara SC arm and in 35.4% (n=104/294) of patients in the DPd/DVd arm.
    • The median number of prior LOT for both arms, Tec-Dara SC and DPd/DVd, was 2 (range 1-3).
    • In the Tec-Dara SC arm, 5.2% (n=15) of patients had prior exposure to an anti-CD38 antibody compared to 5.4% (n=16) of patients in the DPd/DVd arm.
    • The majority of patients in both arms were refractory to any immunomodulatory drug (Tec-Dara SC, 84.9% [n=247]; DPd/DVd, 85.5% [n=253]).
      • Lenalidomide refractory status was observed in 82.5% (n=240) of patients in the Tec-Dara SC arm compared to 84.8% (n=251) of patients in the DPd/DVd arm.
  • At the clinical cut-off date of August 1, 2025, 71% of patients remained on treatment with Tec-Dara SC and 28.3% of patients remained on treatment receiving DPd/DVd.1,2 
    • Discontinuation of treatment was observed in 29% of patients in the Tec-Dara SC arm compared to 71.7% in the DPd/DVd arm primarily due to progressive disease (PD; 7.4% vs 57.9%, Tec-Dara SC vs DPd/DVd).
  • The median duration of treatment was 32.4 months vs 16.1 months for Tec-Dara SC vs DPd/DVd, respectively.1 
  • The median relative dose intensity for TECVAYLI was 97.1% and 90-97.8% for daratumumab across groups.1 
  • A dose reduction of TECVAYLI occurred in 28.5% of patients who received ≥1 dose of TECVAYLI with most occurring in Cycle 7+.1 
  • Cycle delays occurred in 87.6% (n=248) vs 64.1% (n=186) of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.2 

Efficacy

Progression Free Survival (PFS)
  • The estimated 36-month PFS was 83.4% (95% CI, 78.2-87.4) vs 29.7% (95% CI, 23.6-36) for Tec-Dara SC vs DPd/DVd (HR, 0.17; 95% CI 0.12-0.23; P<0.001), respectively, resulting in significantly lower risk of disease progression or death.1 
    • The median progression free survival (mPFS) was not reached (NR) in the Tec-Dara SC arm vs 18.1 months in the DPd/DVd arm.
    • Additionally, PFS benefit was observed consistently across all prespecified and clinically relevant patient subgroups, including age ≥75 years (HR, 0.35; 95% CI, 0.14-0.89), prior anti-CD38 (HR, 0.19; 95% CI, 0.05-0.67), lenalidomide refractory (HR, 0.17; 95% CI, 0.12-0.24), baseline ISS stage III (HR, 0.31; 95% CI, 0.12-0.79), high-risk cytogenetics (HR, 0.15; 95% CI, 0.09-0.25), ≥60% bone marrow plasma cells (HR, 0.17; 95% CI, 0.07-0.43), and soft tissue plasmacytomas (HR, 0.33; 95% CI, 0.17-0.63).
Response Rates

MajesTEC-3 Treatment Response1,2 

A graph of numbers and a number of data AI-generated content may be incorrect.

Abbreviations: CI, confidence interval; CR, complete response; DPd, daratumumab + pomalidomide + dexamethasone; DVd, daratumumab + bortezomib + dexamethasone; OR, odds ratio; ORR, overall response rate; PR, partial response; RR, relative risk; SC, subcutaneous; sCR, stringent complete response; Tec-Dara SC, teclistamab + daratumumab SC; VGPR, very good partial response.


MajesTEC-3 Response Duration1 
Tec-Dara SC (N=291)
DPd/DVd (N=296)
Median time to first response, months (range)
1.2 (0.9-25)
1.2 (0.7-6.3)
Median time to ≥CR, months (range)
6.9 (1.0-34.5)
6.9 (1.5-18.8)
DOR, median (95% CI)
NE (NE-NE)
23.5 (19.8-29.9)
36-month DORa, % (95% CI)
88.5 (83.7-92)
36.4 (28.9-43.9)
Abbreviations: CI, confidence interval; CR, complete response; Dara, daratumumab; DOR, duration of response; DPd, daratumumab + pomalidomide + dexamethasone; DVd, daratumumab + bortezomib + dexamethasone; NE, not estimable; ORR, overall response rate; SC, subcutaneous; Tec, teclistamab.
aThis is based on patients who achieved an ORR: Tec-Dara SC, n=259; DPd/DVd, n=223.
Minimal Residual Disease (MRD) Negativity
  • In the next-generation sequencing (NGS) primary analysis set, MRD negativity (10-5) rate was 58.4% (153/262) vs 17.1% (46/269; risk ratio [RR], 3.43; 95% CI, 2.58-4.55) for Tec-Dara SC vs DPd/DVd, respectively.1,2 
    • Additional MRD negativity analyses are described below:
      • Primary analysis set: MRD negativity (10-5) ≥CR: 57.6% (151/262) vs 17.1% (46/269; OR, 6.54; 95% CI, 4.37-9.77) for Tec-Dara SC vs DPd/DVd, respectively.
      • Primary analysis set: MRD negativity (10-6) ≥CR: 53.8% (141/262) vs 10.4% (28/269; OR, 9.70; 95% CI, 6.11-15.42) for Tec-Dara SC vs DPd/DVd, respectively.
      • Primary analysis set: Sustained (≥6 months) MRD negativity (10-5) ≥CR: 46.6% (122/262) vs 11.2% (30/269; OR, 6.78; 95% CI, 4.31-10.64) for Tec-Dara SC vs DPd/DVd, respectively.
      • Primary analysis set: Sustained (≥6 months) MRD negativity (10-6) ≥CR: 39.3% (103/262) vs 6.3% (17/269; OR, 9.20; 95% CI, 5.31-15.95) for Tec-Dara SC vs DPd/DVd, respectively.
      • Evaluable set: MRD negativity (10-5) ≥CR: 89.3% (150/168) vs 63% (46/73; OR, 5.01; 95% CI, 2.51-9.98) for Tec-Dara SC vs DPd/DVd, respectively.
      • Evaluable set: MRD negativity (10-6) ≥CR: 87.5% (140/160) vs 41.8% (28/67; OR, 9.61; 95% CI, 4.81-19.20) for Tec-Dara SC vs DPd/DVd, respectively.
Overall Survival (OS)
  • At 36 months, the estimated OS rates were 83.3% (95% CI, 78.3-87.2) vs 65% (95% CI, 58.8-70.5) in the Tec-Dara SC arm vs DPd/DVd arm, respectively.1 
    • At 6 months and 30 months post-treatment, 92.2% and 84.3% of patients were alive in the Tec-Dara SC arm, respectively, while 94.5% and 69.6% of patients were alive in the DPd/DVd arm, respectively.
Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Total Symptom Score
  • The estimated 36-month event-free rate for symptom worsening of MySIm-Q total symptom score was 75.6% (95% CI, 68.1-81.6) vs 63.3% (95% CI, 54.7-70.6) in the Tec-Dara SC arm vs DPd/DVd arm (HR, 0.50; 95% CI, 0.34-0.72; P<0.001), respectively.1 

Safety

MajesTEC-3 Safety Results1

A screenshot of a computer screen AI-generated content may be incorrect.

Abbreviations:COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; Dara, daratumumab; DPd, daratumumab + pomalidomide + dexamethasone; DVd, daratumumab + bortezomib + dexamethasone; SC, subcutaneous; TEAE, treatment-emergent adverse event; Tec, teclistamab; URTI, upper respiratory tract infection.
aThe safety population included all patients who received study treatment.
bMost common TEAEs of any grade were defined as those occurring in ≥30% of patients in either treatment group; most common grade 3/4 TEAEs were defined as those occurring in ≥10% of patients in either treatment group.

  • Serious AEs occurred in 70.7% vs 62.4% of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively, with the most common being pneumonia (Tec-Dara SC, 16.6%; DPd/DVd, 13.1%).1 
  • Treatment discontinuation due to TEAEs was observed in 4.6% vs 5.5% of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.1 
  • Cytokine release syndrome (CRS) occurred in 60.1% of Tec-Dara SC patients, all of which were grade 1 (44.2%) or grade 2 (15.9%).1,2 
    • Median duration of CRS events was 2 days (range, 1-22) with all resolving and none leading to treatment discontinuation.
    • Most CRS events occurred during SUD (SUD 1, 33.9%; SUD 2, 30%) with no grade 2 events reported following cycle 1.
    • Supportive measures for CRS treatment were utilized in 56.9% of Tec-Dara SC patients with 29.3% of patients receiving tocilizumab.
  • Immune effector cell-associated neurotoxicity syndrome (ICANs) occurred in 1.1% of Tec-Dara SC patients (grade 1, n=2; grade 4, n=1) with all events resolving and the grade 4 event leading to discontinuation of TECVAYLI.1 
  • Infections of any grade occurred in 96.5% vs 84.1% of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.1 
    • Of these, grade 3/4 infections occurred in 54.1% vs 43.4% of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.
    • After 6 months of treatment, new-onset grade ≥3 infections decreased, which aligned with the transition to monthly dosing.
    • The incidence of any grade, grade 3/4, and serious COVID-19 infections and COVID-19 pneumonia was higher among patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively, and detailed below. MajesTEC-3 trial enrollment was initiated during the COVID-19 pandemic, prior to the establishment of optimal infection prevention approaches in patients receiving B-cell maturation antigen (BCMA)-directed therapy.
      • Any grade COVID-19 infection: 43.8% vs 33.4%
      • Any grade COVID-19 pneumonia: 12% vs 4.1%
      • Grade 3/4 COVID-19 infection: 6% vs 2.1%
      • Grade 3/4 COVID-19 pneumonia: 11.3% vs 2.4%
      • Serious COVID-19 infection: 6.7% vs 2.1%
      • Serious COVID-19 pneumonia: 11.3% vs 2.8%
    • Fatal infections occurred in 4.6% (n=13) vs 1.4% (n=4) of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.
        • Of the 13 infection deaths in the Tec-Dara SC arm, 12 occurred ≤6 months following treatment initiation and prior to the implementation of reinforced protocol-specified immunoglobulin replacement. Of note, immunoglobulin replacement was not administered to 9 of these 12 patients.
  • Hypogammaglobulinemia was reported in 84.5% (n=239) vs 60.3% (n=175) of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.1 
    • 87.3% (n=247) and 44.8% (n=130) of patients received ≥1 dose of immunoglobulin therapy in the Tec-Dara SC arm and DPd/DVd arm, respectively.
  • Second primary cancer was observed (Tec-Dara SC, 12.4% [n=35]; DPd/DVd, 8.6% [n=25]).1,2 
    • Most cases were cutaneous or noninvasive (Tec-Dara-SC, 8.1% [n=23]; DPd/DVd, 4.5% [n=13]).
  • Death occurred in 15.9% (n=45) vs 33.1% (n=96) of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively, mainly due to TEAEs (Tec-Dara SC, 7.1% [n=20]; DPd/DVd, 5.9% [n=17]) and PD (Tec-Dara SC, 4.6% [n=13]; DPd/DVd, 20.3% [n=59]).1,2 
    • Deaths due to TEAE related to study treatment as assessed by the investigator occurred in 4.2% (n=12) vs 1.7% (n=5) of patients in the Tec-Dara SC arm vs DPd/DVd arm, respectively.

Pharmacokinetics and Immunogenicity

  • Trough serum concentrations of teclistamab increased with 1.5 mg/kg weekly, remained steady with 3 mg/kg every 2 weeks, then declined with 3 mg/kg monthly.1 
  • Trough serum concentrations of daratumumab in the Tec-Dara SC arm were comparable to those in the DPd/DVd arm.1
  • Anti-teclistamab or anti-daratumumab antibodies were detected in <1% of patients.1 

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 09 December 2025.

 

References

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1 Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. [published online ahead of print December 09, 2025]. N Engl J Med. 2025. doi:10.1056/nejmoa2514663.  
2 Costa LJ, Bahlis NJ, Perrot A, et al. Supplement to: Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. [published online ahead of print December 09, 2025]. N Engl J Med. 2025. doi:10.1056/nejmoa2514663.