A Randomized Phase II Study of Subcutaneous Mosunetuzumab in Combination With Polatuzumab Vedotin Compared With Rituximab Plus Polatuzumab Vedotin in Patients With Relapsed or Refractory Large B‐Cell Lymphoma

ABSTRACT Mosunetuzumab plus polatuzumab vedotin has shown promising activity versus rituximab plus polatuzumab vedotin (R‐Pola) in patients with relapsed/refractory (R/R) large B‐cell lymphoma (LBCL; NCT03671018). We present results from the Phase II randomized cohort, evaluating subcutaneous mosunetuzumab plus polatuzumab vedotin (Mosun‐Pola), with > 2 years of follow‐up. Patients with R/R LBCL and ≥ 1 prior line of therapy were randomized to receive Mosun‐Pola or R‐Pola. Mosunetuzumab was administered subcutaneously with Cycle (C) 1 step‐up dosing (5/45/45 mg) then 45 mg on C2 Day (D) 1–C8D1 (21‐day cycles). Polatuzumab vedotin (1.8 mg/kg) was given intravenously (IV) on D1 of C1–6. Rituximab IV (375 mg/m 2 ) was given on D1 of C1–8. Primary endpoint was best objective response rate (ORR). As of November 15, 2024, 80 patients had been enrolled (Mosun‐Pola, n = 40; R‐Pola, n = 40). Best ORR was 77.5% (95% confidence interval [CI] 61.6–89.2) for Mosun‐Pola and 50.0% (95% CI: 33.8–66.2) for R‐Pola; complete response (CR) rates were 55.0% (95% CI: 38.5–70.7) and 35.0% (95% CI: 20.6–51.7), respectively. Median progression‐free survival was 25.4 months for Mosun‐Pola and 6.4 months for R‐Pola (hazard ratio [HR] 0.47); median overall survival was not reached and 25.5 months (HR: 0.78), respectively. Cytokine release syndrome occurred in 12.5% of Mosun‐Pola‐treated patients (all Grade 1/2). Fixed‐duration Mosun‐Pola demonstrated benefit across all efficacy endpoints compared with R‐Pola in patients with R/R LBCL. These findings are consistent with the observed benefit of Mosun‐Pola for patients with R/R LBCL in the global Phase III SUNMO study (NCT05171647). Trial Registration: Clinicaltrials.gov number: NCT03671018