First-in-human study of in vivo CAR-T therapy GT801 in adults with relapsed or refractory CD19-positive B-cell hematologic malignancies.

7079 Background: Despite high initial cure rates, patients with B-cell hematologic malignancies, including B-ALL and B-NHL, experience substantial relapse, with markedly reduced disease-free and overall survival after second-line therapy. GT801 is a first-in-human, in vivo CAR-T therapy that uses antibody-displayed lipid nanoparticle (LNP) to deliver CD19 CAR mRNA directly to T cells, enabling in vivo reprogramming without ex vivo cell manufacturing or lymphodepletion. We report initial safety and efficacy data from an open-label, single-arm phase I study (NCT07205315). Methods: GT801 was evaluated using a modified 3+3 dose-escalation design across three dose levels (0.5, 1.5, and 3.0 mg). Patients received up to 4 treatment cycles, each consisting of a single intravenous administration of GT801 on Day 1 of a 7-day cycle. 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), assessed per Lugano 2014 criteria. Results: As of January 13, 2026, 3 patients were enrolled (median age 60 years; median three prior therapies). One patient received 3 doses at 0.5 mg, and two patients received 4 doses at 1.5 mg. All patients had B-NHL. Premedication included dexamethasone, NSAIDs, antihistamines. Most AEs were Grade 1-2. Common TEAEs included cytokine release syndrome (CRS), cytopenia, and transient liver enzyme elevations. Grade ≥3 events were hematologic toxicities and CRS. No neurotoxicity or organ failure was observed. At Week 4, all patients demonstrated a treatment response. Peripheral blood flow cytometry showed rapid CAR-T generation, with CD8 + CAR-T cells detectable within 4 hours post-infusion and peak levels on Day 1. Reprogramming efficiency reached up to 93% and was maintained with repeat dosing. Minimal off-target CAR expression was detected in monocytes. Complete peripheral B-cell depletion occurred within 4 hours after the first dose and was sustained for at least 7 days; after the third dose, B-cell depletion and CAR-T detection were observed in both peripheral blood and bone marrow. Conclusions: GT801 demonstrated a manageable safety profile and early signs of antitumor activity in heavily pretreated B-NHL patients. The ability to generate functional CAR-T cells in vivo without lymphodepletion supports further clinical evaluation of GT801 as a promising therapeutic approach. Clinical trial information: NCT07205315 . Research sponsor: Vivacta Biotechnology (Shanghai) Co., Ltd.