MajesTEC-3: Randomized, phase 3 study of teclistamab plus daratumumab versus investigator’s choice of daratumumab, pomalidomide, and dexamethasone or daratumumab, bortezomib, and dexamethasone in patients with relapsed/refractory multiple myeloma.

Abstract

TPS8072 Background: Patients (pts) with relapsed/refractory multiple myeloma (RRMM) after prior therapy with a proteasome inhibitor (PI) and lenalidomide are challenging to treat. Daratumumab in combination with pomalidomide and dexamethasone (DPd) or bortezomib and dexamethasone (DVd) are approved for pts with RRMM; however, disease control could be further improved. There is an unmet need for new therapeutic options with different modes of action. Teclistamab (tec; JNJ-64007957) is a B-cell maturation antigen (BCMA) × CD3 bispecific antibody that redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. In the phase 1, MajesTEC-1 study (NCT03145181), tec monotherapy was well-tolerated and showed encouraging efficacy in heavily pretreated pts with RRMM. The combination of tec and daratumumab (tec-dara) in the phase 1b TRIMM-2 study (NCT04108195) was also well-tolerated with promising efficacy. MajesTEC-3 (NCT05083169) is a multicenter, open-label, randomized phase 3 study that will compare the efficacy of tec-dara versus investigator’s choice of DPd or DVd in pts with RRMM. Methods: Pts (≥18 years old) must have documented MM per International Myeloma Working Group (IMWG) criteria; measurable disease; Eastern Cooperative Oncology Group performance status 0–2; received 1–3 prior treatment (tx) lines, including a PI and lenalidomide (pts with 1 prior tx line must be lenalidomide-refractory); with progressive disease on or after their last tx (or within 60 days of completing lenalidomide). Pts who received prior BCMA-directed tx or who are refractory to an anti-CD38 monoclonal antibody will be excluded. ̃560 pts will be randomized 1:1 to receive 28-day cycles of tec-dara or investigator’s choice of DPd or DVd (stratified by investigator’s choice of DPd or DVd, ISS stage, and number of lines of prior tx). Step-up doses of tec will be given prior to the first tx dose. Dara, DPd and DVd will be administered per approved schedules. Pts will be treated until disease progression, death, intolerable toxicity, withdrawal of consent or end of study, whichever occurs first. Response will be assessed per 2016 IMWG criteria. The primary endpoint will be progression-free survival (PFS). Secondary endpoints include overall response rate, complete response or better, MRD negativity, PFS on next-line tx (PFS2), overall survival, and incidence and severity of AEs. Adverse events (AEs) will be graded by Common Terminology Criteria for AEs v5.0, except for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which will be graded by American Society for Transplantation and Cellular Therapy guidelines. The study opened in October 2021 and enrollment is ongoing. Clinical trial information: NCT05083169.