A Phase 1/2 clinical trial (NCT06481735) is currently underway to assess the potential of allogeneic Power3 knock-out CD19 CAR-T cell therapy in patients battling relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). This innovative approach, which modifies T cells from healthy donors, aims to improve treatment outcomes for this challenging patient population.
The study leverages the concept of tonic signaling in CAR-T cells by disabling the Power3 gene. This modification is designed to enhance the persistence of the CAR-T cells and improve their overall response to the treatment. The trial is structured in two phases: a dose-escalation phase (Phase 1) and an expansion cohort phase (Phase 2).
Phase 1: Dose Escalation and Safety Evaluation
Phase 1 of the trial will enroll between 6 and 18 participants. These patients will receive one of three dose levels of the allogeneic Power3 knock-out CD19 CAR-T cell therapy: 1 × 10^6 cells/kg, 3 × 10^6 cells/kg, or 6 × 10^6 cells/kg. The dose escalation follows a "3 + 3" design, where three subjects are enrolled in each cohort. If one subject experiences a dose-limiting toxicity (DLT), three additional subjects will be enrolled at the same dose level to further evaluate safety. To ensure patient safety, the administration of the CAR-T cell therapy is staggered by 28 days between the first two subjects in each cohort, and before moving to the next cohort.
The primary objectives of Phase 1 are to evaluate the tolerability and safety of the allogeneic Power3 knock-out CD19 CAR-T cells in patients with relapsed/refractory B-ALL and to determine the recommended Phase 2 dose (RP2D).
Phase 2: Efficacy Assessment
In Phase 2, 10 to 12 subjects will be enrolled and receive the cell infusion at the RP2D, which will be determined based on the maximum tolerated dose (MTD), the occurrence of DLT, efficacy results, pharmacokinetics/pharmacodynamics, and other data obtained during Phase 1. The primary objective of Phase 2 is to evaluate the efficacy of the allogeneic Power3 knock-out CD19 CAR-T cell therapy in this patient population.
This trial represents a significant step forward in the development of novel CAR-T cell therapies for B-ALL. By utilizing allogeneic cells and incorporating the Power3 knock-out strategy, researchers aim to overcome some of the limitations associated with traditional CAR-T cell therapies, such as manufacturing challenges and potential for T cell exhaustion.
