Subcutaneous Teclistamab in Combination with Daratumumab for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma: Results from a Phase 1b Multicohort Study

Introduction: Teclistamab (Tec) is a B-cell maturation antigen × CD3 T-cell redirecting bispecific antibody. In the phase 1 MajesTEC-1 trial in patients (pts) with heavily pretreated relapsed/refractory multiple myeloma (RRMM), Tec monotherapy was well tolerated and yielded an overall response rate of 65% and very good partial response or better rate of 58% at the recommended phase 2 dose (RP2D) with 6.1 months' median follow-up; responses were durable and deepened over time. Daratumumab (Dara) is a monoclonal antibody that targets CD38 and is approved for the treatment of MM. In addition to direct cytotoxicity, Dara has immunomodulatory effects, including promotion of T-cell expansion and depletion of suppressive CD38+ immunoregulatory cells, making it a rational partner for T-cell redirection. In preclinical studies, the lytic activity of Tec against MM cell lines was enhanced by pretreatment and combination treatment with Dara. By targeting discrete yet complementary antigens, combination of Tec and Dara may improve efficacy in pts with RRMM. We present data for pts with RRMM who received Tec + Dara in a phase 1b multicohort study (TRIMM-2; NCT04108195).