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8007 Background: The BCMA × CD3 bispecific antibody teclistamab (tec; JNJ-64007957) redirects CD3+ T cells to mediate T-cell activation and subsequent lysis of BCMA-expressing myeloma cells. The multicohort, open-label, phase 1/2 MajesTEC-1 study is investigating safety/efficacy of tec in patients (pts) with RRMM who previously received ≥3 lines of therapy (LOT). In phase 1, the recommended phase 2 dose (RP2D) of tec was identified as a weekly subcutaneous dose of 1.5 mg/kg preceded by step-up doses of 0.06 and 0.3 mg/kg. Initial results from pts treated with the tec RP2D in phase 1/2 (no prior exposure to an anti–BCMA-targeted treatment), demonstrated that tec was well tolerated with encouraging efficacy. Here we present updated results from pts treated at the RP2D, including additional pts and longer follow-up. Methods: Eligible pts were aged ≥18 years, had documented MM (per IMWG criteria), and had received ≥3 prior LOT including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Prior BCMA-targeted therapy was not permitted in Phase 1. Pts received tec at the RP2D. The primary endpoint was overall response rate (assessed per IMWG 2016 criteria). Adverse events (AEs) were graded per CTCAE v4.03 (cytokine release syndrome [CRS] and ICANS graded per ASTCT guidelines). Data cutoffs for safety and efficacy (N = 165) were Sep 7 and Nov 9, 2021, respectively. Results: Median pt age was 64 y (range 33–84); 58% were male, and median prior LOT was 5 (range 2–14); 100% were triple-class exposed, 70% were penta-drug exposed, 78% were triple-class refractory, and 30% were penta-drug refractory. ORR was 64% (95% CI 56–72), with a complete response or better achieved in 30% of pts. Responses were durable and deepened over time; median duration of response (DOR) was not reached. The 12-mo DOR rate was 66% (95% CI 49–79). The majority of pts who responded to treatment in the first cycle had a reduction in soluble BCMA. The most common hematologic AEs were neutropenia (65%; grade 3/4: 57%), anemia (50%; grade 3/4: 35%), thrombocytopenia (38%; grade 3/4: 21%), and lymphopenia (34%; grade 3/4: 32%). Infections occurred in 104 pts (63%; grade 3/4: 35%). The most common nonhematologic AE was CRS (72%; grade 3: 0.6%; no grade 4/5); median time to CRS onset (range) was 2 days (1–6) and median duration was 2 days (1–9). Five pts (3%) reported a total of 9 ICANS events (all grade 1/2; 7 were concurrent with CRS; all resolved). There were no treatment-related deaths. No pts required a teclistamab dose reduction due to AEs. Conclusions: Current data with ̃9 months of follow-up reaffirm the deep and durable responses that have been observed with tec in pts with highly refractory MM, with no new safety signals. Additional data with longer follow-up, including subgroup analyses and PFS, will be presented. Clinical trial information: NCT04557098.