Safety and efficacy of CD7-CAR-T cell in patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma: Phase I dose-escalation/dose-expansion study.
Authors: Lijuan Hu, Hui Yu, Heng Mei, Dehui Zou, Yaqing Li, Danying Liao, Wei Liu, Yan Xu, Lei Zhang, Xudong Zhang, Zhenchang Sun, Xinhua Wang, Min Wang, Fengtao You, Huimin Meng, Tian Wang, Bozhen Zhang, Lin Yang, Mingzhi Zhang, Xiaojun Huang
Journal: Journal of Clinical Oncology (2024)

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 .