MajesTEC-9: A phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM).

7507 Background: Triplet and quadruplet regimens have greatly improved outcomes in newly diagnosed multiple myeloma, yet a high unmet need remains for more effective, broadly accessible treatments for anti-CD38- and lenalidomide- (Len) exposed/refractory RRMM. Teclistamab (Tec) is the most widely used BCMA×CD3 BsAb in heavily pretreated RRMM, with improved outcomes in earlier lines of therapy (LOTs). In MajesTEC-3, the synergistic Tec-daratumumab combination significantly improved progression-free and overall survival (PFS/OS) as early as first relapse. MajesTEC-9 (NCT05572515) is the first phase 3 study of Tec monotherapy in pts with 1–3 prior LOTs. Methods: Pts with RRMM and 1–3 prior LOTs including anti-CD38 and Len were randomized 1:1 to receive 28-day cycles (C) of Tec (C1–2: 2 step-up doses then 1.5 mg/kg QW; C3–6: 3 mg/kg Q2W or Q4W depending on response; C7+: 3 mg/kg Q4W) or investigator’s choice of PVd/Kd (21/28-day C). Primary endpoint was PFS by IRC; secondary endpoints included OS, complete response or better (≥CR), and safety. Results: 593 pts were randomized (Tec, n=296; PVd/Kd, n=297). Median (range) age: 70 (34–86) yrs; number of prior LOTs: 2 (1–3); Len refractory: 80%; anti-CD38 refractory: 85%; refractory to last LOT: 92%. With 17.3-mo median follow-up, Tec significantly improved PFS vs PVd/Kd (HR, 0.29; 95% CI, 0.23–0.38; P