High complete response rate with TNB-486 in relapsed/refractory follicular lymphoma: Interim results from an ongoing phase 1 study.

7524 Background: Follicular lymphoma (FL) is incurable with a relapsing/remitting pattern and decreasing progression-free survival (PFS) interval per recurrence. In the relapsed/refractory (R/R) setting, patients (pts) failing CAR T or CD20 bispecific T-cell engagers (TCE) have few options. TNB-486 is a novel bispecific CD19xCD3 TCE that induces T-cell–mediated cytotoxicity with reduced cytokine release via a low-affinity αCD3 moiety. We present interim data from a phase 1 dose-escalation study of TNB-486 (NCT04594642). Methods: Third-line+ R/R FL pts (grade [G] 1–3a) were enrolled (prior CD19 therapy allowed). Escalating fixed TNB-486 doses (0.03–2.4 mg) without priming were evaluated prior to implementing single (day [D] 1) and double priming doses (D1 & 8) prior to target dose (D15). TNB-486 was given IV every 2 weeks in 28-d cycles (C) for up to 2 y. Response was assessed with RECIL 2017 by central image review. Adverse events (AEs) and CRS/ICANS were graded by CTCAE v5.0 and 2019 ASTCT criteria. Results: As of Dec 31, 2022, 17 pts received TNB-486 at target doses 0.03–10 mg (median age 68 y [range 33–86]; 53% male; 65% stage III/IV; 25% CD20 − disease; median prior lines of therapy [LOT] 3 [range 2–9]). Prior therapies included αCD20 Ab (100%), alkylator (76%), IMiD (47%), CD20 TCE (12%), CD19 CAR T (12%), and ASCT (6%); 53% progressed or started 2 nd LOT within 24 mo of initiating 1 st LOT (POD24). Median time on study was 7 mo (range 1–22). Eleven pts were response evaluable for efficacy at target doses ≥2.4 mg. Objective response rate (ORR) and complete response (CR) rate were 91% (Table). ORR/CR for pts with CD20 − disease, prior CD20 TCE, and POD24 was 100%. One pt progressed at C6 with preserved CD19 expression; all others remain in remission to date. The 6-mo PFS rate was 91%. No G3+ CRS occurred (59% G1, 12% G2). Neurologic events consistent with ICANS were reported in 24%, all G1–2 except 1 with a G3 event (confusion). All CRS/NT were transient, resolving in a median of 1.5 d (range 1–5). G3+ treatment-related AEs in >10% of pts included decreased lymphocytes (35%) and neutropenia (12%). No treatment-related deaths or AEs leading to discontinuation occurred (1 pt died and 1 discontinued due to COVID-19). One pt received double step-up priming dosing to date with no CRS/NT. Conclusions: TNB-486 induces high complete remission rates during early phase dose escalation. With limited follow-up, responses appear durable in heavily pretreated FL pts, with a manageable safety profile. Dose escalation is ongoing to identify the RP2D. Clinical trial information: NCT04594642 . [Table: see text]