The first-in-human, universal chimeric receptor antigen (CAR) T-cell (CAR-T) therapy GC027 was tolerable and resulted in antileukemic responses among patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL), according to results from a phase 1 trial presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting I 2020.1

The universal CAR T cells target CD7, which, according to Xinxin Wang, PhD, of Gracell Biotechnologies Co, Ltd, in China, and lead author and presenter of the study, “is a good target for T-ALL because it is expressed by more than 95% of T-ALL patients.”

GC027 is allogeneic, which may prevent the development of graft-versus-host disease. The product is introduced using lentivirus for rapid elimination of T-ALL cells. Preclinical studies showed efficacy in a T-ALL xenograft model, and this prospective study evaluated the safety and efficacy in humans.

The single-arm, open-label study treated 5 adult patients with relapsed/refractory CD7-positive T-ALL with a single infusion of 1 of 3 different dose levels of G027: 0.6 x 107/kg, 3 x 107/kg, and 1.5 x 107/kg. Lymphodepletion therapy was administered prior to the G027 infusion. The primary endpoint was safety and the secondary endpoints included objective response rate (ORR) within 3 months after G027 infusion.

Patients with extramedullary or central nervous system disease were excluded. At baseline, the median age was 24 (range, 19-38). Patients were heavily pretreated, with 5 median number of prior therapies (range, 1-9). Two patients had high-risk disease and the median bone marrow tumor burden was a median of 38.2% of blasts. None of the patients had undergone a prior allogeneic hematopoietic stem cell transplant.

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All patients developed cytokine release syndrome (CRS), 4 of which were grade 3 and 1 was grade 4. All cases were manageable and resolved with treatment and supportive care. None of the patients developed neurotoxicity.

The complete remission (CR)/CR with incomplete hematologic recovery was 100%. By day 28, 4 patients achieved a CR with negative for minimal residual disease (MRD) and 3 of these patients remained MRD negative up to day 161. One patient achieved CR but was MRD positive, and relapsed by day 29.

Peak CAR T-cell expansion in peripheral blood occurred between week 1 and 2.

“As the first-in-human, universal CAR T-cell therapy for adult relapsed/refractory T-ALL,” Dr Wang said, “GC027 has demonstrated superior clinical efficacy and induced deep response in patients with acceptable safety profile.” She added that trial enrollment is ongoing.

Reference

Wang X, Li S, Gao L, et al. Clinical safety and efficacy study of TruUCAR™ GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Presented at: American Association for Cancer Research (AACR) Virtual Annual Meeting I; April 27-28, 2020. Abstract CT052.

This article originally appeared on Cancer Therapy Advisor