Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors

Summary

Claudin18.2(CLDN18.2) is a kind of integrin membrane protein in the tight junction between epithelium and endothelium, which is highly expressed in many solid tumors, especially in gastric cancer and pancreatic cancer. The CLDN18.2/PD-L1 dual-targeting CAR-T will be investigated in patients with CLDN18.2-positive advance solid tumors.

Eligibility

Inclusion Criteria:

1. Male or female, Age 18-75 years old;
2. Patients with pathologically/histologically confirmed diagnosis of solid tumors (such as advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and pancreatic adenocarcinoma) have received at least once systemic standard treatment and disease progressed; or refused/ cannot tolerate the subsequential standard treatment after the first line treatment;
3. Must have CLDN18.2-positive tumor expression ≥10% as determined by the CLDN18.2 IHC assay;
4. Estimated life expectancy \> 3 months (according to investigator's judgement);
5. At least 1 measurable lesion per RECIST 1.1;
6. The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
7. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
8. Patients should have reasonable CBC counts, renal and hepatic functions;
9. No other serious diseases (autoimmune diseases or any immune deficiency disease);
10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion;
11. Men must be willing to use effective and reliable method of contraception and are not allowed to donate sperm for at least 12-months after T-cell infusion;
12. Voluntarily participate in the research, understand and sign the informed consent.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;
3. Any uncontrolled active infection;
4. Patients who have clinically significant thyroid dysfunction;
5. Patients who have received prior cellular therapy such as CAR T, TCR, tumor-infiltrating lymphocytes;
6. Patients who are allergic to immunotherapy or any associated drugs, such as cytokines and the preconditioning regimen (cyclophosphamide, fludarabine);
7. Patients with untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
8. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
9. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment;
10. Patients with active autoimmune diseases, history of autoimmune diseases or other diseases in need of immunosuppressive therapy;
11. Patients with major surgery or injury less than 4 weeks prior to leukapheresis or plan to have major surgery during the research period;
12. Patients with second malignancies in addition to targeted malignancies within 5 years before screening;
13. Patients with unstable/active ulcer or digestive tract bleeding;
14. Patient suffering from diseases that affect the signing of written informed consent or compliance with research procedures; or are unwilling or unable to comply with research requirements;
15. Patients who have a history or a tendency for digestive tract bleeding;
16. Patients who are inappropriate to participate in this research as considered by PI.

Conditions2

Interventions1

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