Safety and efficacy of GT719, an off-the-shelf CAR-NKT therapy, in adults with relapsed or refractory CD19-positive B-cell malignancies.

7078 Background: GT719 is an off-the-shelf CAR-NKT therapy derived from umbilical cord blood hematopoietic stem cells and genetically engineered to co-express an anti-CD19 CAR, an invariant natural killer T (NKT)-specific TCR, and secreted interleukin-15 (IL-15). This design enables CD19-targeted tumor killing, avoids risk of graft-versus-host disease (GVHD), and enhanced cellular expansion, persistence, and immune function through IL-15 signaling. We report clinical data from 7 adults with relapsed or refractory (R/R) CD19-positive B-cell hematologic malignancies enrolled in two open-label, single-arm studies (NCT06948981, NCT07131254) evaluating the safety and preliminary efficacy. Methods: The primary endpoint was safety, including treatment-emergent adverse events (TEAEs), graded per CTCAE v5.0. Secondary endpoints included 3-month overall response rate (ORR), best overall response (BOR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Efficacy was assessed using Lugano 2014 criteria and the 2024 Chinese guidelines for adult acute lymphoblastic leukemia. Results: As of December 31, 2025, 7 patients were treated (median age 51 years; median two prior therapies), including 3 with B-ALL and 4 with B-NHL. Following FC lymphodepletion, all patients received a single GT719 infusion (5×10⁷ to 1×10⁹ viable cells). Most adverse events (AEs) were Grade 1-2. Grade ≥3 AEs were limited to lymphodepletion-related cytopenia and resolved or improved to Grade ≤2 within 14 days, excluding disease-related cytopenia. One patient experienced Grade 1 cytokine release syndrome that resolved within 1 day. No ICANS, neurotoxicity, or GVHD, severe infections, or serious TEAEs were observed. Efficacy was evaluable in all patients across B-ALL, follicular lymphoma (FL, grade 3a), and diffuse large B-cell lymphoma (DLBCL). The 3-month ORR was 50% (3/6), with all responders achieving CR; one patient was excluded due to insufficient follow-up. The disease control rate (DCR) was 71.4% (5/7). Two of 3 FL patients achieved CR, while one had a PR and remained under follow-up. One of three B-ALL patients achieved stringent complete remission, maintained through 24 weeks of relapse-free follow-up. CAR transgene analysis demonstrated robust in vivo expansion, with peak levels occurring between Days 7-10 in B-ALL and within two months in FL. GT719 persistence was observed for up to six months post-infusion. Conclusions: GT719 demonstrated a favorable safety profile and encouraging antitumor activity in adults with R/R CD19-positive B-cell malignancies. The absence of severe GT719-related toxicities and evidence of durable cellular persistence support further clinical investigation of this off-the-shelf CAR-NKT therapy. Clinical trial information: NCT06948981 , NCT07131254 . Research Sponsor: Grit Biotechnology.