IBCL-373: Updated Experience from Mosunetuzumab in Multiple Relapsed Follicular Lymphoma: Promising Efficacy from a Phase I Trial

Context Follicular lymphoma (FL) often presents with recurrent relapses. Treatment options for patients (pts) with FL who have received ≥2 prior lines of therapy are limited, and prognosis is poor. The safety and efficacy of mosunetuzumab, a full-length, fully humanized IgG1 CD20/CD3 bispecific antibody is currently being investigated in an ongoing open-label, multicenter, Phase I/Ib, dose-escalation and expansion trial in relapsed/refractory (R/R) B-cell lymphoma (GO29781; NCT02500407). Objective To present updated data from the R/R FL cohort. Methods Pts received intravenous mosunetuzumab step-up doses in cycle (C) 1, days (D) 1 and 8, then the target dose on D15 and D1 of each subsequent 21-day cycle (Group B); treatment continued for ≤17 cycles. Results As of January 21, 2020, mosunetuzumab 0.4/1.0/2.8 mg to 1/2/13.5 mg (C1D1/8/15 dose levels) was given to 62 pts with FL who received ≥2 prior systemic therapies. Pts had a median age of 59 (27–85) years, median number of 3 (2–11) prior therapies; 33 pts (53%) were double refractory, 30 (48%) had progression of disease within 24 months of first-line treatment (POD24), and four (6%) received prior chimeric antigen receptor T-cell (CAR-T) therapy. Overall response rate (ORR) and CR rate were 68% and 50%, respectively. In high-risk pts, consistent CR rates were observed: 55% (18/33) in pts with double refractory disease, 53% (16/30) in pts who had POD24, 78% (7/9) in pts with PI3Ki refractory FL, and 50% (2/4) in those who received prior CAR-T therapy. Twenty-six pts with a CR (74%) remained in remission (median time on study: 14.4 months). In responders (n=42), median duration of response was 20.4 months (95% CI: 11.7–not reached), and median progression-free survival was 11.8 months (95% CI: 7.3–21.9). Adverse events (AEs) and serious AEs were reported in 60 (97%) and 22 pts (35%), respectively. The most common grade (Gr) ≥3 AEs included hypophosphatemia (23%) and neutropenia (21%). Fourteen pts (23%) experienced CRS1; events were mostly Gr 1 or 2, reversible, and occurred largely during C1. Conclusions A high CR rate, durable responses, and a manageable safety profile were observed with mosunetuzumab monotherapy in heavily pre-treated pts with FL, including high-risk pts.