Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Talquetamab is a humanized IgG4PAA bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). Teclistamab is a humanized IgG4PAA bispecific antibody designed to target B cell maturation antigen (BCMA) and the CD3 molecule found on T cells. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Rationale for combining talquetamab and teclistamab is that, these agents promote the activation of T cells and induce myeloma cell lysis mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells and daratumumab induces lysis of CD38-expressing tumor cells by a number of mechanisms, including complement-dependent cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), through activation of complement proteins, natural killer (NK) cells, and macrophages, respectively. This study consists 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as last study assessment for last participant in study. Total duration of study is up to 1 year and 6 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.
The purpose of this study is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1) and to characterize the safety of the RP2R(s) for the study treatment (Part 2). The RP2R(s) will describe the combination doses and schedules of (tal+tec+dara) the treatment combinations to be pursued in Phase 2.