Polatuzumab Vedotin-Piiq

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

Novel, accessible treatment options, are needed for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Mosunetuzumab, a T-cell–engaging bispecific antibody, plus polatuzumab vedotin, an antibody–drug conjugate, (Mosun-Pola), represents a novel fixed-duration outpatient therapy. The phase III SUNMO study (NCT05171647) demonstrated superior efficacy of Mosun-Pola versus rituximab plus gemcitabine-oxaliplatin (R-GemOx) in patients with R/R LBCL, with a manageable safety profile. We report outcomes of a Japan subgroup analysis of the SUNMO study.

Patients were randomized 2:1 to receive Mosun-Pola or R-GemOx. Dual primary endpoints were centrally assessed overall response rate and progression-free survival (PFS).

At data cutoff (February 17, 2025), of 208 patients randomized (Mosun-Pola, n  = 138; R-GemOx, n  = 70), 16 were enrolled from Japan (Mosun-Pola, n  = 9; R-GemOx, n  = 7). All patients receiving Mosun-Pola achieved a response (100% [ n  = 9]) versus 57.1% (n = 4/7) for those receiving R-GemOx. PFS was significantly prolonged with Mosun-Pola; median PFS of 16.2 months versus 3.8 months with R-GemOx (hazard ratio: 0.42; 95% confidence interval: 0.07–2.63). In the safety-evaluable population (Mosun-Pola, n  = 9; R-GemOx, n  = 7), overall incidence of adverse events was similar between the Japan subgroup and the overall population across both treatment arms. Cytokine release syndrome occurred in 5 patients who received Mosun-Pola; all events were grade 1, and all resolved. No incidence of immune effector cell-associated neurotoxicity syndrome was reported.

Mosun-Pola demonstrated promising efficacy and manageable safety in patients with R/R LBCL enrolled from Japan, which was comparable with the overall population, supporting Mosun-Pola as a potential new treatment option in this patient population.

ClinicalTrials.gov, NCT05171647.