A Randomized Phase II Study of Subcutaneous Mosunetuzumab in Combination With Polatuzumab Vedotin Compared With...

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/m²) 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.