Dual-targeting CAR-T therapy for advanced cancer patients with pleural or peritoneal metastases

A Phase Ia/Ib, Open-label, Single-arm, Dose-escalation and Expansion Study of Specific Dual-targeting VEGFR1 and PD-L1 CAR-T in Cancer Patients With Pleural or Peritoneal Metastases

This study is testing a new type of CAR-T therapy that targets specific proteins in advanced cancer patients with tumors in the pleural or peritoneal cavities to see if it helps them when other treatments haven't worked.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT05477927 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a novel dual-targeting CAR-T therapy that targets VEGFR1 and PD-L1 in patients with advanced cancers exhibiting serosal cavity metastases, such as ovarian, breast, lung, and gastric cancers. The approach involves injecting CAR-T cells directly into the pleural or peritoneal cavities of patients who have not responded to standard treatments. The study consists of two parts: a dose escalation phase to assess safety and a subsequent dose expansion phase to evaluate effectiveness based on observed responses. The safety and efficacy will be measured using established clinical criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with advanced serosal cavity metastases from specific cancers who have failed standard treatments.

Not a fit: Patients with early-stage cancers or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve treatment outcomes and quality of life for patients with advanced cancers and serosal cavity metastases.

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

Eligibility criteria

Inclusion Criteria:

1. Male or female, Age 18-65 years old; negative results of serum or urine pregnancy test within 48 hours before treatment are needed to provide for fertile women (or women who have undergone sterilization or at least 2 years after menopause can be regarded as infertile);
2. Patients diagnosed as ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, etc., accompanied by serous cavity metastasis, have received systemic standard treatment, and have clinical symptoms of serous cavity metastasis;
3. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;
4. Estimated life expectancy ≥ 3 months (according to investigator's judgement);
5. Absolute neutrophil count ≥ 1.5×10\^9/L, platelet count ≥ 90×10\^9/L, absolute lymphocyte count ≥1×10\^8/L, hemoglobin ≥ 9.0 g/dL;
6. Creatinine clearance rate ≥60 mL/min, Serum ALT/AST≤2.5 times of the normal level, and total bilirubin≤1.5 times of the normal level;
7. Cardiac ejection fraction ≥50%, no pericardial effusion;
8. No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy);
9. Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment;
10. Patients must take reliable contraceptive measures before entering the trial, during the research process until 1 year after CAR-T infusion; reliable contraceptive measures will be determined by the main investigator or designated personnel;
11. Voluntarily participate in the research, understand and sign the informed consent;
12. The side effect of the last anti-tumor treatment was reduced to ≤1 grade, except for hair loss.

Exclusion Criteria:

1. Had accepted any treatment of CAR-T therapy;
2. Allergic to cytokines; uncontrolled activity infection;
3. Acute or chronic (graft-versus-host disease) GVHD;
4. Accompanied by other uncontrolled malignant tumors;
5. Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;
6. Other uncontrolled diseases in active period that hinder participation in the trial;
7. Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;
8. Patients with grade 2-3 hypertension or poorly controlled;
9. History of mental illness that is difficult to control;
10. Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy;
11. The existing medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or the administration of the study drug from the point view of PI;
12. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy;
13. Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends;
14. Female subjects of childbearing age were reluctant to accept high-efficiency contraceptive measures during the treatment period or within 1 year after the treatment ends;
15. Patient suffering from diseases that have signed written informed consent or comply with research procedures; or are unwilling or unable to comply with research requirements;
16. Patients who are inappropriate to participate in this experiment 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: XIA HE, Ph.D

Conditions Malignant Peritoneal Effusion; Malignant Ascites; Serous Cavity Metastatises; CAR-T regional injection; Solid Tumors; Serosal Cavity metastases