This is a multicenter, open-label, Phase 1/2 master protocol evaluating autologous dual-target CAR-T cell therapy in adults with advanced solid cancers. After central biomarker screening, each participant is assigned the best-matched dual-target construct from a predefined target-pair library. The trial is designed to test whether biomarkerguided dual targeting can improve tumor control, reduce antigenescape risk, and preserve safety in solid tumors.
Participants undergo central pathology review and antigen profiling on fresh or archived tumor tissue. If one or more predefined dual-target pairs qualify, a target-selection committee ranks candidate pairs using (1) co-expression level, (2) tumor-normal differential, (3) diseasespecific biologic rationale, and (4) product / manufacturing feasibility. All enrolled participants receive lymphodepletion with fludarabine and cyclophosphamide followed by one infusion of the assigned autologous dual-target CAR-T product. Each newly activated target-pair cohort begins with dose escalation (modified 3+3 lead-in) and, if acceptable, proceeds to dose expansion at the recommended Phase 2 dose / schedule (RP2D / RP2S). Optional repeat infusion is allowed for selected participants with retained eligibility, available product, and no prohibitive toxicity. Disease response is assessed by RECIST 1.1 for non-CNS disease and by RANO for CNS cohorts. Participants are followed for disease outcomes for 24 months and for long-term genemodified cell safety for up to 15 years, consistent with local genetherapy follow-up expectations. Because the solid-tumor target landscape continues to evolve, this example uses a broad predefined target library rather than claiming to be a permanently exhaustive list of every future target.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
72
Autologous dual-target CAR-T cells are patient-derived T cells engineered to recognize two tumor-associated antigens selected from a predefined target library. In clinical trials, they are administered to enhance tumor targeting and reduce antigen escape, with evaluation of safety, tolerability, and preliminary anti-tumor activity.
chemotherapy preconditioning regimen used before cell therapy to reduce the patient's existing lymphocytes and create space for infused cells. In clinical trials, it is given prior to CAR-T infusion to enhance cell expansion, persistence, and overall treatment efficacy.
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGDose-limiting toxicities (DLTs)
Time frame: 28 Days
Incidence and severity of treatment-emergent adverse events
Time frame: 12 Months
Objective response rate (ORR) by RECIST 1.1 or RANO
Time frame: 24 Months
Disease control rate (DCR)
Time frame: 24 Months
Duration of response (DoR)
Time frame: 24 Months
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Cyclophosphamide lymphodepletion is a chemotherapy preconditioning regimen administered prior to cell therapy to suppress existing immune cells and improve the environment for infused cells. In clinical trials, it is given before CAR-T infusion to support cell expansion, persistence, and enhance therapeutic effectiveness.