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 (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).^1,2
  • Guo et al (2024)³ presented the pharmacokinetics (PK), pharmacodynamics, and anticancer activity of TECVAYLI 1.5 mg/kg every other week (Q2W) and the PK of TECVAYLI 3 mg/kg every 4 weeks (Q4W) using population PK and quantitative systems pharmacology (QSP) modeling. In 63 responders who switched to Q2W dosing in MajesTEC-1, no apparent 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 1,000 virtual patients estimated that steady-state PK parameters were comparable between the 1.5 mg/kg Q2W and 3 mg/kg Q4W doses.

POPULATION PHARMACOKINETIC simulations - majestec-1 study

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: 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.^1,2

Guo et al (2024)³ presented the PK, pharmacodynamics, and anticancer activity of TECVAYLI 1.5 mg/kg Q2W and the PK of TECVAYLI 3 mg/kg Q4W using population PK and QSP modeling.

Study Design/Methods

• TECVAYLI PK was evaluated using a population PK model.
• An exposure-response analysis was conducted to evaluate the DOR, PFS, and OS.
• TECVAYLI PK at steady state was simulated for the 1.5 mg/kg Q2W and 3 mg/kg Q4W doses using the population PK model.
• A multiscale QSP model assessed the effect in responders of switching to Q2W dosing on concurrent engagement of B-cell maturation antigen (BCMA) on target multiple myeloma (MM) cells and CD3 on effector T cells, to form a target cell-biologic-effector cell (TBE) trimer.
  • Trimers were formed by the BCMA-TECVAYLI dimer binding to unbound CD3 or by the CD3-TECVAYLI dimer binding to unbound BCMA.
  • Virtual patients who maintained response for 6 cycles were simulated with either continuous 1.5 mg/kg weekly (QW) dosing or with a switch to 1.5 mg/kg Q2W dosing.

Results

Population PK Analysis

• Median estimated TECVAYLI trough concentration (C_trough) was lower after switching from QW to Q2W dosing, 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 to 1.5 mg/kg Q2W.

Exposure-response Analysis

• In 63 responders who switched to Q2W dosing in MajesTEC-1, no apparent exposure-response trend was observed between TECVAYLI exposures and DOR, PFS, and OS. See Figure: MajesTEC-1 Study: Exposure-Response Trend: TECVAYLI C_trough After First Q2W Dose and DOR, PFS, or OS.

QSP Model Validation and Simulation

• A switch from QW to Q2W had minimal impact on TBE trimer formation. Estimated DOR and median reduction in tumor volume over time were noted to be comparable between QW and Q2W scenarios.

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 TECVAYLI PK parameters, including maximum concentration, C_trough, and area under the curve were estimated to be comparable between the 1.5 mg/kg Q2W and 3 mg/kg Q4W doses. See Figure: MajesTEC-1 Study: Comparable Estimated Steady State TECVAYLI PK With 1.5 mg Q2W vs 3 mg/kg Q4W.

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 10 December 2024.