TECVAYLI - MajesTEC-5 Study - TECVAYLI-Based Regimens

Summary

• Johnson & Johnson does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by regulatory agencies.
• MajesTEC-5 is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY^®-based combination regimens in patients with transplant-eligible (TE), newly diagnosed multiple myeloma (NDMM).¹ 
  • Raab et al (2026)¹ published the updated safety and efficacy results of TECVAYLI in combination with DARZALEX FASPRO^® and lenalidomide (Tec-DR) and TECVAYLI in combination with DARZALEX FASPRO, bortezomib, and lenalidomide (Tec-DVR) in patients with TE-NDMM from 3 induction cohorts of the MajesTEC-5 study with outcomes reported through the pre‑maintenance treatment period at a median follow‑up of 12.3 months (range, 3.1-14.5).

PRODUCT LABELING

• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;  https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.

CLINICAL DATA - MAJESTEC-5 STUDY

MajesTEC-5 (NCT05695508) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY-based combination regimens in patients with TE-NDMM.¹ 

Study Design/Methods

• The study design is presented in Figure: MajesTEC-5 Study Design.

Raab et al (2026)¹ published the updated safety and efficacy results of Tec-DR and Tec-DVR in patients with TE-NDMM from 3 induction cohorts of the MajesTEC-5 study at a median follow-up of 12.3 months (range, 3.1-14.5).

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• Patients were enrolled at 11 sites in Germany.
• A total of 49 patients were included in this study (arm A, n=10; arm A1, n=20; arm B, n=19). See Table: MajesTEC-5 Study: Baseline Characteristics and Demographics.
• The median follow-up duration by the premaintenance treatment timepoint, defined as the interval from the first dose of study treatment to the last visit before initiation of maintenance, was 12.3 months overall (arm A, 11.9 months; arm A1, 12.5 months; arm B, 12.2 months).
• A total of 93.9% of patients (n=46) completed all 6 planned induction cycles. The median duration of induction therapy was 7 months (range, 2.5-13.2).

Safety

• Treatment-emergent adverse events (TEAEs) reported in the 3 induction cohorts are presented in Table: MajesTEC-5 Study: Summary of TEAEs (≥25% in Any Arm).
• Grade 3/4 TEAEs were reported in 91.8% of patients (n=45). No grade 5 TEAEs were reported.

Treatment Modification and Discontinuation

• Cycle delays were reported in 90% of patients (n=9) in arm A, 75% of patients (n=15) in arm A1, and 73.7% of patients (n=14) in arm B during the induction phase.

Infections

• Any-grade infections were reported in 81.6% of patients (n=40) overall.
  • The most commonly reported infections (>10% in any treatment arm) were upper respiratory tract infection (URTI; 40.8% [n=20]), coronavirus disease 2019 (COVID-19; 20.4% [n=10]), nasopharyngitis (14.3% [n=7]), pneumonia (8.2% [n=4]), viral URTI (8.2% [n=4]), respiratory tract infection (6.1% [n=3]), infection (6.1% [n=3]), and bronchitis (4.1% [n=2]).
• Grade 3/4 infections were reported in 36.7% of patients (n=18) overall.
• No grade 5 infections were reported in any arms.
• Cytomegalovirus reactivation was the only opportunistic infection reported, and it occurred in 6.1% of patients (n=3); all cases resolved, and viremia was documented without evidence of end-organ involvement.
• By the pre-maintenance treatment timepoint, 91.8% of patients (n=45) had experienced ≥1 hypogammaglobulinemia TEAE or had a post‑baseline immunoglobulin G (IgG) level <400 mg/dL.
• Administration of intravenous immunoglobulin (IVIG) was reported in 89.8% of patients (n=44).
• Prior to initiation of study treatment, acyclovir was administered for herpes zoster prophylaxis in 100% of patients (n=49), and a sulfamethoxazole-trimethoprim regimen for Pneumocystis jirovecii pneumonia prophylaxis was received by 93.9% of patients (n=46).

Cytokine Release Syndrome and Neurotoxicity

• Cytokine release syndrome (CRS) was reported in 67.3% of patients (n=33), with the majority of events occurring during the step-up dosing period.  
• All CRS events were grade 1/2, resolved with management, and did not result in discontinuation of study treatment.
• At least one any-grade neurologic TEAE was reported in 61.2% of patients (n=30), with most events being low-grade (maximum severity grade 1/2 in 57.1% of patients; grade 3 in 4.1% of patients).
  • Peripheral sensory neuropathy was the most frequently reported neurologic event, occurring in 20.4% of patients (n=10; 12 total events), and all cases were grade 1/2.
  • By treatment arm, peripheral sensory neuropathy was reported in 10% of patients (1/10; maximum grade 1) in arm A, 25% of patients (5/20; maximum grade 1) in arm A1, and 21.1% of patients (4/19; grade 1, n=1; grade 2, n=3) in arm B.
  • No treatment‑related immune-effector cell-associated neurotoxicity syndrome (ICANS) events were reported.
  • In addition, no cases of cranial nerve palsy, acute demyelinating neuropathy, transverse myelitis, or movement or neurocognitive disorders were reported.

Serious TEAEs

• Serious TEAEs were reported in 55.1% (n=27) of patients overall.
  • The most common serious TEAEs (≥2 patients in any arm) were pyrexia (12.2% [n=6]), CRS (8.2% [n=4]), rash (6.1% [n=3]), and febrile neutropenia (6.1% [n=3]). Acute kidney injury, COVID-19, and infection were each reported in 4.1% (n=2) of patients.
• By the pre-maintenance treatment timepoint, discontinuations due to TEAEs were observed for individual treatment components. One patient in arm A1 discontinued TECVAYLI, 3 patients in arm B discontinued bortezomib, and 4 patients discontinued lenalidomide (arm A1, n=1; arm B, n=3).
• Of note, no TEAEs resulted in discontinuation of all agents (Tec-DR or Tec-DVR) within the assigned treatment regimen.

Efficacy

• Summary of response outcomes is shown in Table: MajesTEC-5 Study: Summary of Best Overall Response.
• At a median follow-up of 12.3 months (range, 3.1-14.5) for the combined arms, no progression events were reported in arms A, A1, and B.
• The efficacy analysis set included 10 patients in arm A, 20 patients in arm A1, and 19 patients in arm B.

Overall Minimal Residual Disease-Negative Response (All Arms Combined)

• In the combined cohort (n=49), the cumulative minimal residual disease (MRD)negative complete response rate per International Myeloma Working Group (IMWG) criteria was 91.8% (arm A, n=10/10; arm A1, n=18/20; arm B, n=17/19).
  • MRD testing was available for 48/49 patients (arm A, n=10/10; arm A1, n=20/20; arm B, n=18/19); all evaluable samples were MRD negative by next-generation flow cytometry (NGF), corresponding to a cumulative MRD‑negativity rate of 98%.
  • One patient in arm B was not evaluable for MRD at any timepoint due to discontinuation prior to completion of induction cycle 3.
• See Tables: MajesTEC-5 Study: Summary of MRD Negativity Rate by the Pre-Maintenance Visit for additional details.

MRD Status – Post-ASCT

• No MRD conversion events were reported after autologous stem cell transplantation (ASCT) and before maintenance therapy.

MRD Status – Pre-Maintenance

• At the pre‑maintenance timepoint, MRD‑negativity rates at the 1×10^-5 threshold were 90% in arm A, 80% in arm A1, and 78.9% in arm B.
• At this timepoint, eight patients were not tested (arm A, n=1; arm A1, n=3; arm B, n=4), and 1 patient in arm A1 was indeterminate.

Stem-Cell Mobilization

• Among patients who received ≥1 study treatment dose of TECVAYLI (N=49), successful stem-cell mobilization was reported in 95.9% of patients (n=47).
• Among patients who underwent stem‑cell mobilization (n=47), mobilization with cyclophosphamide and granulocyte colony-stimulating factor was reported in 95.7% of patients (n=45), and use of plerixafor for mobilization was reported in 42.6% (n=20).
• Stem-cell mobilization was not performed in 2 patients: 1 patient withdrew consent after cycle 3 and 1 patient did not proceed due to cytopenia and insufficient circulation of CD34+ cells.
• The overall median total CD34+ stem‑cell yield was 8.1×10⁶/kg (range, 2.6-15.9), with protocol‑specified minimum and ideal target yields of 2.5×10⁶/kg and 5×10⁶/kg, respectively.
• Among patients with successful stem-cell mobilization (n=47), autologous stem‑cell transplantation was performed in 87.8% of patients (n=43).
• Among patients who underwent high-dose therapy and ASCT, the median time to neutrophil engraftment was 12 days, and the median time to platelet engraftment was 14 days.

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 16 July 2026.