Abstract
Background: In a pivotal Phase II study (NCT02500407), subcutaneous (SC) mosunetuzumab (Mosun), a CD20xCD3 T-cell engaging bispecific antibody, achieved high response rates and durable remissions, and demonstrated pharmacokinetic non-inferiority to the intravenous (IV) formulation in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy, including those with high-risk features (Bartlett et al. ASH 2024; Hess et al. EHA 2025). We report updated efficacy and safety data from the pivotal Phase II study of Mosun SC in pts with R/R FL after three years of follow-up.
Methods: Pts had R/R FL Grade (Gr) 1–3a and ≥2 prior therapies. Fixed-duration Mosun SC was administered (≤1mL volume) in 21-day cycles with step-up dosing in Cycle (C)1 (C1 Day [D]1, 5mg; C1D8, 45mg; C1D15, 45mg; C2D1 onwards, 45mg). Hospitalization was not mandatory. Pts with a complete response (CR) by C8 completed treatment without additional cycles; those with a partial response or stable disease could continue therapy for up to 17 cycles. Pts who achieved a CR with initial treatment and relapsed after the end of treatment were eligible for re-treatment. Responses were assessed per Cheson 2007 criteria. CR rate, overall response rate (ORR), duration of (complete) response (DO[C]R), progression-free survival (PFS) and overall survival (OS), and safety endpoints were investigator-assessed. Time to next treatment (TTNT) and response to re-treatment were exploratory endpoints.
Results: Ninety-four pts were enrolled in this pivotal cohort; median age was 65 years (range: 35–84), 87% had Ann Arbor Stage III/IV disease, 66% were refractory to prior anti-CD20 therapy, 43% had progressed within 24 months from start of first-line treatment (POD24), 30% had elevated lactate dehydrogenase, and 23% had bulky disease (>7cm). As of May 1, 2025, median follow-up was 35.5 months (range: 1–48).
The ORR and CR rate in the overall population were 74% and 63%, respectively. Median DOR and DOCR were 25.1 months (95% confidence interval [CI]: 21–39) and 33.6 months (95% CI: 22–not estimable [NE]), respectively. Median PFS was 18.5 months (95% CI: 11–28) and median OS was not reached (95% CI: NE); the estimated 30-month PFS and OS rates were 37% (95% CI: 27–48) and 83% (95% CI: 75–91), respectively. Median TTNT was 39.7 months (95% CI: 36–NE).
In 59 pts with a CR, the 30-month PFS and OS rates were 56% (95% CI: 42–69) and 92% (95% CI: 85–100), respectively, and median PFS was 35.9 months (95% CI: 25–NE). Of 9 pts re-treated with Mosun, 7 (78%) responded, and 6 (67%) achieved a CR. At the clinical cut-off date, 4/7 re-treated pts with a response remained in remission.
In pts with POD24, the ORR and CR rates were 70% and 58%, respectively. Median PFS was 15.7 months (95% CI: 6–NE) and the 30-month PFS rate was 41% (95% CI: 25–57). In pts with bulky disease, the ORR was 68% and CR rate was 55%. Median PFS was 28.3 months (95% CI: 6–NE) and the 30-month PFS rate was 42% (95% CI: 18–66), though few pts remained at risk.
No new cytokine release syndrome (CRS) events or fatal, serious, or Gr ≥3 adverse events (AEs) were reported since the previous analysis. Injection site reactions remained the most common AE (69%). Fatal AEs occurred in 5 pts (COVID-19 pneumonia, n=2; COVID-19, n=1; hemophagocytic lymphohistiocytosis, n=1 [with active Epstein-Barr virus, cytomegalovirus, and lymphoma transformation]; general physical health deterioration, n=1). CRS events occurred in 30% of pts (Gr 3: n=2) and all resolved. Infections were reported in 55% of pts (Gr 1/2: 36%; Gr 3/4: 16%; Gr 5: 3%). Gr 3 febrile neutropenia was reported in 2 pts. No immune effector cell-associated neurotoxicity syndrome events were reported. The safety profile during re-treatment was consistent with initial therapy, with only 2 (10%) Gr 1 CRS events, 1 serious AE, and no fatal AEs.
Conclusions: In this updated analysis, with a median follow-up of 35.5 months, fixed-duration Mosun SC continued to demonstrate durable responses, similar to those previously reported for Mosun IV in a comparable patient population. The safety profile was manageable with low rates of CRS and infections, consistent with previous analyses. Mosun SC has a favorable benefit-risk profile with the convenience of outpatient accessibility and short administration times.
