Three-year follow-up of the Phase 1 first-in-human study investigating surovatamig, a novel CD19xCD3 T-cell engager, in patients with Relapsed/Refractory (R/R) follicular lymphoma (FL)

Abstract Introduction: Surovatamig (formerly AZD0486) is a novel, IgG4 fully human CD19xCD3 bispecific T-cell engager (TCE) being evaluated in an ongoing phase 1 study in patients (pts) with R/R B-cell non-Hodgkin lymphoma (B-NHL) (NCT04594642). Here, we present long-term follow-up data of surovatamig in pts with R/R FL. Methods: Eligible pts had R/R CD19+ B-NHL and ≥2 prior lines of therapy (pLOT), which could include prior CD19 CAR T-cell therapy (CAR T) or CD20 TCEs. Escalating target doses of surovatamig were administered intravenously, with no step-up dosing (SUD), single SUD, or double SUD schedules in cycle 1, followed by target doses every 2 weeks in 28-day cycles for up to 24 months. Pts with 2 consecutive complete responses (CRs) could receive dosing every 4 weeks after cycle 6. The primary objective was to assess safety, tolerability, and pharmacokinetics and determine the recommended phase 2 dose (RP2D). Response was assessed by central imaging review per RECIL 2017 criteria. Minimal residual disease (MRD) was assessed by PhasED-Seq using Foresight CLARITY for Lymphoma test in plasma circulating tumor DNA. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per 2019 ASTCT criteria and adverse events (AEs) by CTCAE v5.0. Results: As of May 19, 2025, 61 pts with R/R FL received surovatamig at target doses up to 15 mg, including 23 at the RP2D of 7.2 mg. The median number of pLOT was 3 (range, 2–11), with 18 (30%), 9 (15%), and 9 (15%) pts having received 3, 4, and ≥5 pLOT, respectively. Fifty-five (90%) pts had prior alkylator therapy, 37 (61%) had prior R-CHOP, 26 (43%) had prior lenalidomide-based therapy, 7 (11%) had prior CAR T, and 5 (8%) had prior CD20 TCE therapy. Overall response rate and CR rate for evaluable pts receiving doses ≥2.4 mg (n=52) were96% and 92%, respectively. Of 41 pts with CR evaluable for MRD, 93% (38/41) achieved undetectable MRD. For pts who received ≥2.4 mg, median duration of follow-up was 16 months (range, 1–47), with estimated 12-month rates of progression-free survival and duration of response of 88% and 91%, respectively. There have been no observed relapses among the 8 pts who had previously progressed after CD20 TCE therapy and/or CD19 CAR T and achieved CR with surovatamig. All 11 pts who completed 24 months of surovatamig treatment remain in CR off therapy. Among the 43 pts who received a double SUD schedule, CRS was observed in 51% (49% grade 1; 2% grade 2) and there were 2 cases of ICANS (grades 1 and 2). The most common (≥5%) grade ≥3 AEs in all 61 pts with FL were neutropenia (20%), hypertension (8%), lymphopenia (7%), and pneumonia (7%). Infections not related to COVID-19 were reported in 38% of pts; late infections occurring beyond 12 months on therapy were predominantly low grade (8% of pts had grade ≥3). Hypogammaglobulinemia was observed in 23% of pts. No pts discontinued due to treatment-related AEs. Conclusion: Surovatamig treatment is well tolerated and results in a high CR rate that is durable in pts with heavily pretreated R/R FL, including those with prior exposure to CD19 CAR T or CD20 TCEs. A phase 2 study of surovatamig monotherapy in pts with FL and ≥2 pLOT (NCT06526793) and a phase 3 study investigating surovatamig in combination with rituximab in pts with treatment-naive FL are underway (NCT06549595).