Safety and efficacy of CD7-CAR-T cell in patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma: Phase I dose-escalation/dose-expansion study.

6515 Background: Patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are clinically manifested by rapid disease progression, poor prognosis and lack of therapeutic options. There is an urgent need to develop other effective modalities. Apart from its expression in normal T and NK cells and no expression in other tissue cells, CD7 is highly expressed in T-ALL/LBL cells. Therefore, CD7 is considered a potential target for the development of CAR-T therapy for T-ALL/LBL. The challenge, however, is to avoid fratricide caused by the expression of CD7 in T cells. We developed a CAR-T cell injection based on CD7 nano antibodies, named PA3-17 injection, by blocking the expression of CD7 molecule on the surface of T cells through anti-CD7 protein expression blocker (PEBL) and evaluate the safety, efficacy and Recommended Phase II Dose (RP2D) of PA3-17 Injection in patients with r/r T-ALL/LBL in a phase I clinical study. Methods: The clinical study (NCT05170568) adopted a "3+3" dose escalation schema and proceed cohort expansion. T-ALL/LBL patients who met the inclusion/exclusion criteria were deployed by entering three dose groups (DL: 0.5×10 6 , 2×10 6 , 4×10 6 CAR-T/kg) to evaluate the initial safety, efficacy and dose-limited toxicities (DLTs). All patients were treated with lymphodepleting chemotherapy pre-treatment before CAR-T cell infusion. The primary endpoints were DLTs and maximum tolerable dose (MTD). Results: As of Nov 28th, 2023, a total of 12 patients were enrolled (3 patients in dose 1, 2, 3 group, 3 patients in RP2D group), all of whom received a single infusion of PA3-17 injection and completed a 28- day DLTs assessment. The median age of enrolled patients was 33.5 years (range 20-64), and 25.0% (3/12) of patients had previously received hematopoietic stem cell transplantation. No DLTs occurred. The RP2D was 2×10 6 CAR-T/kg. The safety analysis showed that 83.3% (10/12) of patients developed cytokine release syndrome (CRS), of which 25% (3/12) had grade 3, and no grade 4 CRS occurred, 16.7% (2/12) of patients experienced 1-2 grade of immune effector cell-associated neurotoxicity syndrome (ICANS), and no grade 3 or higher ICANS occurred. The efficacy data showed that the best ORR was 83.3% (10/12) and the CR rate was 75% (9/12). The median follow-up time was 213.5 days. Five patients (Pt 1/5/6/7/9) maintained CR for more than 6 months. One patient (Pt6) had a tumor mass with a diameter greater than 7cm at baseline prior CAR-T infusion but achieved CR 28 days after infusion, then she underwent transplantation at sixth month but died at eighth month because of heart problems, which is unrelated with PA3-17 infusion. Conclusions: PA3-17 injection has shown a good safety profile and encouraging efficacy in r/r T-ALL/LBL patients. RP2D has been determined and the key Phase II clinical study is about to begin. Clinical trial information: NCT05170568 .