Background: Tec is a B-cell maturation antigen × CD3 bispecific antibody currently being evaluated in the single-arm, phase 1/2 MajesTEC-1 trial (NCT04557098) in pts with RRMM who had received ≥3 prior lines of therapy (LOT) and were TCE to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The aim of this study is to evaluate the comparative efficacy of tec versus physician’s choice of therapy, as no head-to-head trials have been conducted. Methods: An external control arm for MajesTEC-1 was created from pts in the long-term follow-up of 4 clinical trials of daratumumab (CASTOR, POLLUX, EQUULEUS, and APOLLO) who met the eligibility criteria for MajesTEC-1. These pts (N = 427) were subsequently treated with physician’s choice of therapy after discontinuing trial txs, and disease progression and best tx response were based on the investigator’s assessment. Individual pt-level data from MajesTEC-1 pts who received tec (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021 were included. Inverse probability of tx weighting (IPTW) with average tx effect on the treated population was used to adjust for imbalances in baseline covariates of prognostic significance: refractory status, progression on last LOT, cytogenetic risk, International Staging System stage, number of prior LOT, extramedullary plasmacytoma, time since diagnosis, age, and hemoglobin. Overall response rate (ORR), rate of complete response or better (≥CR), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), time to next tx (TTNT), and overall survival (OS) were assessed. For binary endpoints (ORR, ≥CR rate, ≥VGPR rate), the relative effect of tec vs physician’s choice of therapy was estimated with an odds ratio (OR) and 95% confidence interval (CI) derived from a weighted logistic regression analysis. A weighted Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% CIs for time-to-event endpoints (PFS, OS, and TTNT). Several sensitivity analyses were conducted. Results: After IPTW, baseline characteristics were comparable between the 2 cohorts. Pts treated with tec had improved outcomes vs physician’s choice of therapy: ORR (OR 4.58; 95% CI 2.83–7.53; P< 0.0001); ≥CR rate (OR 12.62; 95% CI 5.20–38.55; P< 0.0001); ≥VGPR rate (OR 11.64; 95% CI 6.49–21.98; P< 0.0001); PFS (HR 0.62; 95%CI 0.45–0.84; P= 0.0024); TTNT (HR 0.38; 95% CI 0.27–0.52; P< 0.0001); and OS (HR 0.47; 95% CI 0.32–0.69; P= 0.0001). Results were similar for all sensitivity analyses. Conclusions: Tec showed improved efficacy versus physician’s choice of therapy in all clinical outcomes, highlighting its therapeutic potential to address unmet needs in pts with TCE RRMM who received ≥3 prior LOT.