Summary

• Janssen does not recommend any practices, procedures or usage that deviate from product labeling and are not approved by the regulatory agencies.
• MajesTEC-1 is an ongoing, phase 1/2, multicohort study evaluating the
• safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1,2
  • Guo et al (2025)^3,4 published pharmacokinetic (PK), pharmacodynamic (PD), and antitumor activity data derived from population PK, exposure-response, and quantitative systems pharmacology (QSP) analyses. In 63 responders who switched from 1.5 mg/kg QW to 1.5 mg/kg every other week (Q2W) dosing in MajesTEC-1, no significant exposure-response trend was observed between TECVAYLI exposures and duration of response (DOR), progression-free survival (PFS), and overall survival (OS). PK simulations based on TECVAYLI concentration-time profiles in 1000 virtual patients estimated that steady-state PK parameters were comparable between the 1.5 mg/kg Q2W and 3 mg/kg once every 4 weeks (Q4W) doses.

POPULATION PHARMACOKINETIC simulations - majestec-1 study

MajesTEC-1 (MMY1001; NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM after ≥3 prior lines of therapy, including triple-class exposure to a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1,2

Guo et al (2025)^3,4 published PK, PD, and antitumor activity data derived from population PK, exposure-response, and QSP analyses, which support the approval of the TECVAYLI schedule at 1.5 mg/kg Q2W in patients who sustained a ≥CR for ≥6 months, and also provide exposure metrics for TECVAYLI administered Q4W at doses of 1.5 mg/kg or 3 mg/kg.

Study Design/Methods

• TECVAYLI serum trough concentrations (C_trough) were estimated using a population PK model in 63 patients who switched from 1.5 mg/kg weekly (QW) to 1.5 mg/kg Q2W once achieving a partial response or better (≥PR) after ≥4 cycles in phase 1 or ≥CR for ≥6 months in phase 2. Estimates were made before the switch and after the first and fourthTECVAYLI Q2W doses.
• An exposure-response analysis was conducted to evaluate the DOR, PFS, and OS based on the individual estimated C_trough value after the first Q2W TECVAYLI dose (C_{trough,1stQ2Wdose}) based on the population PK analysis results from the 63 responders.
• A QSP model was used to simulate and compare target cell-biologics-effector cell (TBE) trimer levels on target cells and efficacy outcomes in virtual patients with RRMM who either switched to 1.5 mg/kg Q2W TECVAYLI dosing or continued with 1.5 mg/kg QW TECVAYLI dosing.
  • Trimers were formed by the B-cell maturation antigen (BCMA)-TECVAYLI dimer binding to unbound cluster of differentiation 3 (CD3) or by the CD3-TECVAYLI dimer binding to unbound BCMA.
  • A total of 3000 virtual patients were included in the initial simulation. Patients who maintained ≥PR on 1.5 mg/kg QW TECVAYLI dosing for 6 cycles of 28 days each were identified as sustained responders (n=1160).
  • These sustained responders were further simulated under 2 dosing scenarios: continuing with 1.5 mg/kg QW TECVAYLI dosing or switching to 1.5 mg/kg Q2W TECVAYLI dosing.
  • Steady-state TECVAYLI PK and trimer formation were simulated for the 1.5 mg/kg Q2W and 3 mg/kg Q4W or 1.5 mg/kg Q4W TECVAYLI doses.

Results

Population PK Analysis

• Based on the population PK model, individual C_trough values were estimated in 63 responders who switched from QW to Q2W TECVAYLI dosing.
• Median estimated TECVAYLI C_trough values were lower after the first and fourth Q2W TECVAYLI doses than those before the first Q2W TECVAYLI dose but remained above the maximum 90% effective concentration (EC_90,max) of 6.039 μg/mL. Details are provided in Table: MajesTEC-1 Study: Median Estimated TECVAYLI Serum C_trough Prior to and After Switching From 1.5 mg/kg QW Dosing to 1.5 mg/kg Q2W.

Exposure-Response Analysis

• In 63 responders who switched from 1.5 mg/kg QW to 1.5 mg/kg Q2W dosing in MajesTEC-1, no significant exposure-response trend was observed between TECVAYLI exposures and DOR, PFS, and OS.

QSP Model Validation and Simulation

• The QSP model estimated comparable TBE trimer formation, tumor volume reduction, and DOR for responders who switched to 1.5 mg/kg Q2W TECVAYLI dosing vs those who continued 1.5 mg/kg QW TECVAYLI.

Comparison of TECVAYLI PK for 1.5 mg/kg Q2W and 3 mg/kg Q4W Doses

• PK simulations in 1000 virtual patients were based on TECVAYLI concentration-time profiles.
• Steady-state median TECVAYLI PK profiles were estimated to be comparable between the 1.5 mg/kg Q2W and 3 mg/kg Q4W TECVAYLI doses.
• At steady-state, the 3 mg/kg Q4W TECVAYLI dose showed a slightly lower C_trough value and a slightly higher maximum concentration (C_max) value, while maintaining an overall similar area under the curve (AUC) compared with the 1.5 mg/kg Q2W TECVAYLI dose.
• Estimated median TBE trimer formation at steady-state trough with the 3 mg/kg Q4W TECVAYLI dose was <20% lower than that with the 1.5 mg/kg Q2W TECVAYLI dose.
• Dosing regimens using doses lower than the 3 mg/kg Q4W TECVAYLI dose, such as 1.5 mg/kg Q4W, led to a reduced PK exposure compared with the 1.5 mg/kg Q2W TECVAYLI dose. The median steady-state exposure was reduced by 70.1% for C_trough, 34.6% for C_max, and 50.0% for AUC relative to the 1.5 mg/kg Q2W regimen.
  • This lower exposure resulted in a 35.7% decrease in median TBE trimer formation at steady-state trough levels relative to the established 1.5 mg/kg Q2W TECVAYLI dosing in sustained responders.

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 September 2025.