CAR-T therapy targeting CLDN18.2 and PD-L1 for advanced solid tumors

A Phase I, Open-label, Single-arm, Dose-escalation and Expansion Study of Specific Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors

This study is testing a new CAR-T therapy that targets specific proteins in patients with advanced solid tumors, like gastric and pancreatic cancers, who haven't responded well to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: CAR T, immunotherapy, cyclophosphamide, fludarabine, CAR-T
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06084286 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of dual-targeting CAR-T cells that focus on CLDN18.2 and PD-L1 in patients with advanced solid tumors, particularly those with gastric and pancreatic cancers. The study consists of two phases: an initial dose escalation phase involving 9 patients, followed by a dose expansion phase that aims to enroll an additional 20 patients if the initial results are promising. Participants will receive intravenous injections of the CAR-T cells, and both safety and effectiveness will be assessed using established evaluation standards. The trial targets patients who have shown minimal response to standard treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with CLDN18.2-positive advanced solid tumors who have progressed after standard treatments.

Not a fit: Patients with solid tumors that do not express CLDN18.2 or those who have not received prior systemic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced solid tumors that express CLDN18.2.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this dual-targeting approach in solid tumors is relatively novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: YongShen Wang, Prof. — West China Hospital
• Study coordinator: Yao Zeng

Conditions Advanced Solid Tumor; CAR-T cell therapy; Solid Tumors; CLDN18.2-positive