IBCL-249 Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients With Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results From a Phase I/II Study

Context: In a Phase I/II study (NCT02500407), escalating doses of the CD20xCD3 bispecific antibody mosunetuzumab were active and well-tolerated in patients with R/R FL and ≥2 prior therapies. Objective: Report pivotal Phase II expansion results. Participants: All patients had R/R FL (Grade 1–3a) and ≥2 prior therapies, including an anti (a)-CD20 therapy and alkylating agent, and an ECOG PS of ≤1. Interventions: Mosunetuzumab was given intravenously in 21-day cycles with C1 step-up dosing for CRS mitigation (C1D1: 1mg; C1D8: 2mg; C1D15 and C2D1: 60mg; D1 of C3+: 30mg). Hospitalization was not mandatory. Mosunetuzumab was continued for 8 (CR by C8) or 17 cycles (PR/SD by C8). Main Outcome Measures: The primary endpoint was CR rate (best response) by Independent Review. Results: As of March 15, 2021, 90 patients had been enrolled (median age: 60 years; median number of prior therapies: 3); 68.9% were refractory to their last therapy, 78.9% to any prior aCD20 therapy, and 53.3% to any prior aCD20 therapy and alkylating agent (double refractory). 52.2% had POD24. Median follow-up was 12.9 months. ORR (CR/PR) and CR rates in all patients were 78.9% and 57.8%, respectively. Rates were comparable in POD24 (83% and 55%, respectively) and double-refractory patients (69% and 48%). At cut-off, 12-month event-free rates after first response were 65.4% in responders and 80.1% in complete responders. Median PFS was 17.9 months. CRS (44.4% by ASTCT 2019 criteria) occurred primarily in C1 and was predominantly Grade 1–2 (42.2%). Grade 3–4 CRS occurred in 2 patients. No Grade 5 (fatal) CRS events occurred. All CRS events resolved. Other AEs (≥20%) were fatigue (36.7%), headache (31.1%), neutropenia and pyrexia (28.9% each), hypophosphatemia (22.2%), and pruritus (21.1%). Grade 3–4 AEs (≥5%) were neutropenia (26.6%), hypophosphatemia (13.3%), hyperglycemia and anemia (7.8% each), and elevated ALT (5.6%). Grade 5 AEs were malignant neoplasm progression and unexplained death (both events mosunetuzumab unrelated). AEs leading to mosunetuzumab discontinuation occurred in 4 patients (4.4%). Conclusions: Mosunetuzumab induces high CR rates and durable remissions in patients with R/R FL and ≥2 prior therapies. Mosunetuzumab has favorable safety, allowing administration without mandatory hospitalization.