SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• MajesTEC-1 (MMY1001) is an ongoing, phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1-6
  • Cohort A (triple-class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody (mAb).¹
    • Moureau et al (2022)^1,3 published a pharmacokinetic (PK) analysis at a median follow-up of 14.1 months (range, 0.3-24.4) in 165 patients treated with TECVAYLI. At the recommended phase 2 dose (RP2D), serum concentrations (C_max) of TECVAYLI measured during the first 4 cycles were maintained above the upper limit of 90% of maximum TECVAYLI exposure (EC₉₀=6 μg/mL).
  • Cohort C included 40 patients with RRMM, previously treated with a PI, an immunomodulatory agent, an anti-CD38 mAb and anti-B-cell maturation antigen (BCMA)-targeted therapies.⁷
    • Touzeau et al (2024)⁷ published PK analysis at a median follow-up of 28.0 months (range, 0.7-31.1) in 40 patients treated with TECVAYLI. TECVAYLI C_trough values in patients were comparable to those observed in BCMA-treatment-naïve patients, with mean C_trough consistently above the maximal EC₉₀ value from an ex vivo assay.
  • The prophylactic tocilizumab cohort is evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of cytokine release syndrome (CRS) in 24 patients with RRMM.^8,9
    • van de Donk et al (2023)⁸ compared the PK profiles of 8 patients from the phase 1 exploratory prophylactic cohort with those of 40 patients from the MajesTEC-1 phase 1 population treated with TECVAYLI at the RP2D. The timing of induction of cytokines interleukin 6 (IL-6) and IL-10 were compared between the prophylactic tocilizumab cohort and the MajesTEC-1 phase 1 cohort.
  • Other relevant literature are included below for your reference.^10-16

CLINICAL DATA - MAJESTEC-1 STUDY

MajesTEC-1 (MMY1001; NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-6

Study Design/Methods

The main objectives are as follows: part 1 (dose escalation) to determine the RP2D for TECVAYLI; part 2 (dose expansion) to distinguish safety and tolerability of TECVAYLI at the RP2D; part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,2

• Key eligibility criteria:
  • Cohort A: ≥3 prior lines of therapy (LOTs) including a PI, an immunomodulatory drug, and an anti-CD38 mAb, no prior BCMA-targeted therapy use.¹
  • Cohort C: ≥3 prior LOTs, a prior PI, an immunomodulatory drug, and an anti-CD38 mAb, enrolled patients who had prior exposure to BCMA-targeted treatment (chimeric antigen receptor [CAR]-T cell and/or antibody drug conjugate [ADC]).⁷
  • Prophylactic tocilizumab cohort: ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb.⁸

Cohort A

Moreau et al (2022)^1,3 published a PK analysis in 165 patients treated with TECVAYLI at a median follow-up if 14.1 months (range, 0.3-24.4).

Results

• TECVAYLI exposure remained over the target level EC₉₀ of 6 μg/mL (previously determined in an ex vivo cytotoxic assay) with a low peak-to-trough ratio.^1,3
• Serum levels of sBCMA were assessed as a potential marker of tumor burden and response. Within one month of TECVAYLI dosing, total sBCMA decreased in 68% of patients (40 of 59) with a partial response or better. Reduced sBCMA levels were observed in 88% of patients (63 of 72) with a partial response or better in cycles 1-4. Increased sBCMA levels were observed in 96% of patients (27 of 28) with no response to TECVAYLI in cycle 1. Additionally, increased sBCMA levels were observed in 9 patients without a response.
• TECVAYLI treatment induced cytokines and activated T cells, but the response was not correlated to changes in levels of cytokine or T-cell activation. Patients with a response had higher levels of IFN-γ, IL-6, IL-10, IL-2 receptor alfa than those without a response.

Cohort C

Touzeau et al (2024)⁷ published a PK analysis in 40 patients treated with TECVAYLI at a median follow-up of 28.0 months (range, 0.7-31.1).

Results

Pharmacokinetics and Immunogenicity

• TECVAYLI C_trough values in patients were comparable to those observed in BCMA-treatment-naïve patients, with mean C_trough consistently above the maximal EC₉₀ value from an ex vivo assay.
• TECVAYLI serum concentrations at or within 48 hours of CRS onset (including step-up and treatment doses) ranged from 0.070 to 8.99 μg/mL.
  • At a PK data cutoff of June 7, 2023, no clear correlation was observed between CRS events or grade and TECVAYLI concentration; serum levels were comparable in patients with CRS across all grades and in patients without CRS.
  • No serum samples from CRS events were positive for antibodies to TECVAYLI.
• Antibodies to TECVAYLI were not detected in the serum of any of the 36 antidrug antibody-evaluable patients.

Soluble BCMA and Bone Marrow BCMA Expression

• Serum was collected prior to the first TECVAYLI dose, and samples were analyzed for sBCMA.
• Baseline sBCMA serum levels overlapped between Cohort C patients and BCMA-treatment-naïve patients. See Table: MajesTEC-1 Study (Cohort C): sBCMA Levels for additional details.
• On cycle 4 day 1, a total of 78.6% of responders (11 out of 14) had a decrease in sBCMA, while 75% of non-responders (3 out of 4) had an increase in sBCMA after TECVAYLI administration.
• sBCMA reduction was higher in responders to TECVAYLI, although the sample size was limited.
• BCMA expression on multiple myeloma (MM) cells in the bone marrow showed no significant difference in the percentage or level of BCMA expression between patients who had prior anti-BCMA CAR-T or ADC exposure (last prior line or any prior line).

Immune Cell Effects

• Assessments included the impact of prior anti-BCMA CAR-T therapy on the number of T cells and the activation and inhibitory receptor expression on T cells prior to TECVAYLI treatment. B-cell numbers were also evaluated.
• Baseline CD4 and CD8 T-cell numbers trended lower in patients who had received anti-BCMA CAR-T compared with those who received prior BCMA-ADC therapy.
  • Activation markers (CD25 and CD38) and inhibitory receptors (programmed cell death 1 [PD-1], T-cell immunoglobulin mucin family member 3 [TIM-3]) were not upregulated on CD4+ and CD8+ T cells from patients in the prior anti-BCMA CAR-T cohort.
• Patients with prior anti-BCMA therapy did not have lower baseline B-cell numbers compared with anti-BCMA-naive patients at any point during treatment.

Prophylactic Tocilizumab Cohort

van de Donk et al (2023)⁸ compared the PK profiles of 8 patients from the phase 1 exploratory prophylactic cohort with those of 40 patients from the MajesTEC-1 phase 1 population treated with TECVAYLI at the RP2D.

Results

• A PK profile of 8 patients from the phase 1 exploratory prophylactic cohort was compared to 40 patients from the MajesTEC-1 phase 1 population treated at TECVAYLI RP2D. See Figure: MajesTEC-1 Study: TECVAYLI Serum Concentration-Time Profile in Patients Treated With TECVAYLI With or Without Prophylactic Tocilizumab for additional details.
• The timing of induction of cytokines IL-6 and IL-10 were compared between the prophylactic tocilizumab cohort, and the MajesTEC-1 phase 1 cohort treated at RP2D. See Figure: MajesTEC-1 Study: Cytokine Induction in Patients Treated With TECVAYLI With or Without Prophylactic Tocilizumab for additional details.

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 05 November 2025.