Background: Treatment of relapsed/refractory multiple myeloma (RRMM) in patients (pts) previously treated with a proteasome inhibitor (PI) and lenalidomide is challenging. Although daratumumab plus pomalidomide and dexamethasone (DPd), and bortezomib and dexamethasone (DVd) are approved for RRMM, further disease control is still needed. Thus, newer therapeutic options with diverse modes of action are warranted. Teclistamab (tec; JNJ-64007957), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody (Ab), induces T cell activation and subsequent lysis of BCMA-expressing myeloma cells. Results from the phase 1 MajesTEC-1 study (NCT03145181) demonstrated that teclistamab was generally well-tolerated with encouraging efficacy in pts with RRMM who were heavily pretreated. In the phase 1b TRIMM-2 study (NCT04108195), teclistamab plus daratumumab (tec-dara) provided promising efficacy and was also well tolerated.
Aims: To describe MajesTEC-3 (NCT05083169), a phase 3, multicenter, open-label, randomized study comparing the efficacy of tec-dara and investigator’s choice of therapy (DPd or DVd) in pts with RRMM.
Methods: Eligible patients (pts) are ≥18 years of age with documented MM based on the International Myeloma Working Group (IMWG) criteria and have measurable disease, an Eastern Cooperative Oncology Group (ECOG) performance status 0–2, previous exposure to 1–3 lines of treatment (tx) which may include a PI and lenalidomide (of note, pts with 1 prior tx line must be lenalidomide-refractory), and progressive disease status on or following their last tx (or within 60 days of completing lenalidomide). Informed consent form will be signed before the first study-related activity is conducted. Pts who are refractory to an anti-CD38 monoclonal antibody or had prior BCMA-directed tx are excluded. Pts (560 planned) will be randomly assigned (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). Pts will receive dara, DPd, and DVd tx per the approved schedules and will be treated until disease progression, death, withdrawal of consent, intolerable toxicity, or end of study, whichever occurs first. Assessment of responses will be based on 2016 IMWG criteria. The primary endpoint will be progression-free survival (PFS), and secondary endpoints will include overall response rate, complete response or better, MRD negativity, PFS on next-line tx (PFS2), overall survival, and incidence and severity of adverse events (AEs). All reported AEs will be graded as per the Common Terminology Criteria for AEs (CTCAE) v5.0. Immune effector cell-associated neurotoxicity syndrome and cytokine release syndrome will be graded per the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. MajesTEC-3 opened in October 2021 and is currently enrolling pts.
Results: Not applicable
Summary/Conclusion: Not applicable