Relapsed or Refractory Acute Leukemia

The objective of this study is to establish the efficacy, safety, and tolerability of S243249 and to establish the recommended phase 2 dose (RP2D) of S243249 monotherapy in participants with relapsed/refractory (R/R) acute leukemia with select mutations. Phase 1 dose optimization will determine the RP2D to be used in Phase 2 dose expansion. The study will include a screening period, a treatment period consisting of continuous 28-day cycles of treatment, a safety follow-up period and a long-term follow-up period. Participants may undergo blood tests, electrocardiogram (ECG), bone marrow aspirations, vital sign checks, questionnaires, and physical exams.

Relapsed or refractory acute leukemia (R/R AL) is a life-threatening blood cancer with poor outcomes and limited treatment options. PID23 Injection is an innovative in vivo CAR-T therapy that delivers a viral vector encoding three targets (CD19, BCMA, and CD70) directly into patients, enabling their own T cells to generate functional CAR-T cells against leukemia cells. This single-center, single-arm, open-label, dose-escalation study (3 dose levels: 0.8×10⁹, 2×10⁹, and 4×10⁹ TU) plans to enroll 3-18 patients with R/R AL aged 3-75 years, ECOG 0-2, and positive for at least one target. The primary objective is to evaluate safety, tolerability, and determine the recommended dose. Secondary objectives include preliminary efficacy (remission, survival), pharmacokinetics (CAR-T expansion), pharmacodynamics (cytokine changes), and exploratory viral clearance. After a single intravenous infusion, patients are hospitalized for ≥3 weeks, followed by monthly visits for 3 months, then every 3 months for up to 2 years. Enrollment is from May 2026 to May 2027, with follow-up through May 2029. The study is conducted at Zhujiang Hospital of Southern Medical University (PI: Prof. Li Yuhua).