107: Pharmacokinetic & Immunogenicity Results from the China Cohort of the MAJESTEC-1 Study of Teclistamab for Relapsed/refractory Multiple Myeloma

Statement of Purpose, Innovation or Hypothesis: Teclistamab (tec) is the first approved B‑cell maturation antigen-directed×CD3 bispecific antibody with weight-based dosing for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). In the phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098), tec demonstrated rapid, deep, and durable responses with a manageable safety profile. Efficacy and safety in the MajesTEC-1 China cohort were consistent with that of the pivotal recommended phase 2 dose (RP2D) cohort. We report pharmacokinetics (PK) and immunogenicity of tec in the MajesTEC-1 China cohort.

Description of Methods & Materials: Patients in the China cohort had RRMM and had received ≥3 prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody. Patients were given tec (RP2D: 0.06, 0.3, then 1.5 mg/kg subcutaneous weekly), with an option of less frequent dosing if a complete response was maintained for 6 months. Serum samples were analyzed for PK and anti-drug antibodies (ADA) by the electrochemiluminescence immunoassay.

Data & Results: The China cohort enrolled 26 patients. Consistent with the pivotal RP2D cohort, tec mean trough concentrations (C_trough) from cycle 2 day 1 onwards were maintained above the ex vivo maximum EC₉₀ (Girgis et al, Targeted Oncology, 2022) in the China cohort. The observed tec PK data in the China cohort were adequately described by a 2-compartment population PK model with first-order absorption and parallel time-independent and time-dependent (decrease over time) elimination pathways established using data from patients in the pivotal RP2D cohort (Miao et al, Targeted Oncology, 2023), indicating no notable ethnic difference in PK between the China cohort and the pivotal RP2D cohort. The model predicted that exposure metrics following the first and steady state treatment doses of tec in the China cohort overlapped with those in the pivotal RP2D cohort, albeit with an ~40% lower median in the China cohort. This may be explained by differences in population PK model covariate distributions, such as the lower median body weight (58 vs 73 kg) and the higher proportion of ISS Stage III patients (26.9 vs 12.1%) in the China cohort compared with the pivotal RP2D cohort. Because a flat exposure-response relationship was observed in the pivotal RP2D cohort (Miao et al, Targeted Oncology, 2023) and efficacy and safety in the China cohort were consistent with that of the pivotal RP2D cohort, the lower exposure metrics predicted in the China cohort is not considered clinically relevant. Moreover, the predicted overall response rate in the China cohort was similar to that in the pivotal RP2D cohort, by mechanism-based quantitative system pharmacology analysis. Only one patient was identified as positive for tec ADAs in the China cohort. ADAs were transient and had low titer (ie, 20). No impact of ADA on tec PK was observed.

Interpretation, Conclusion or Significance: Overall, the PK and immunogenicity data in the MajesTEC-1 China cohort support using the same dosing regimen of tec recommended for the pivotal RP2D cohort.

Disclosures: All authors are employees of Janssen.

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Additional Information/Authors: Acknowledgments: We would like to acknowledge the following individuals for their contribution: Yang Song, Juanjuan Song, Katherine Chastain, Xinchao Luo, Lin Huang, Hongmei Xu, Deeksha Vishwamitra, Longen Zhou, Binbin Sun, and Yaming Su. This study was funded by Janssen Research & Development, LLC. Medical writing support was provided by Edwin C Thrower, PhD, CMPP, of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC.