Engineered T-cell Therapy for Patients With ALPP-Positive Advanced Solid Tumors

A Single-Arm, Single-Center, Open-Label Pilot Study of Patients With ALPP-Positive Advanced Solid Tumors

This is a single-arm, open-label, dose-escalation clinical trial designed to evaluate the safety, tolerability, expansion, and persistence of ALPP CAR-T cells in patients with ALPP-positive recurrent or metastatic solid tumors who have progressed after prior therapies. The primary objective is to determine the maximum tolerated dose (MTD), with a secondary aim to assess preliminary clinical efficacy in solid tumors.

This study is designed as a single-arm, open-label, single-dose clinical trial to evaluate the safety and efficacy of ALPP CAR-T cell therapy in patients with recurrent or metastatic solid tumors. The study protocol consists of five main stages: (1) patient screening, (2) collection of peripheral blood mononuclear cells (PBMCs), (3) lymphodepletion chemotherapy, (4) ALPP CAR-T cell infusion, and (5) post-infusion follow-up.

Inclusion Criteria:

1. Participants must voluntarily provide written informed consent.
2. Aged 18-70 years (inclusive).
3. Life expectancy ≥ 3 months.
4. ECOG performance status 0-1.
5. Failed or unsuitable for standard therapy.
6. At least one measurable lesion per RECIST 1.1.
7. ALPP-positive tumor confirmed by immunohistochemistry.
8. Adequate organ and bone marrow function.
9. Effective contraception required for participants of childbearing potential.
10. Adequate venous access for leukapheresis.

Exclusion Criteria:

1. Primary CNS malignancy or uncontrolled CNS metastases.
2. Other malignancies within 5 years (except adequately treated non-melanoma skin cancer or carcinoma in situ).
3. Active autoimmune disease or history of autoimmune disease.
4. Immunodeficiency, including HIV positivity.
5. Bleeding disorders (inherited or acquired).
6. Clinically significant cardiovascular disease.
7. Active infection (including tuberculosis, hepatitis B/C, syphilis).
8. Pregnant or breastfeeding women.
9. History of refractory epilepsy, active GI bleeding, or high risk of tumor bleeding.
10. Severe systemic or psychiatric illness.
11. Prior cell or gene therapy.
12. Severe drug hypersensitivity history.
13. Investigator-assessed unsuitability for trial participation.