Dual-targeting HER2 and PD-L1 CAR-T for Cancers With Pleural or Peritoneal Metastasis

Study Overview
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Brief Summary
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Serosal cavity metastasis of malignant tumor is one of the late complications, which seriously affects the quality of life and survival time of patients. HER-2 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors. The HER-2/PD-L1 dual-targeting CAR-T will be investigated in patients with HER2 positive solid tumor serosal cavity metastases.

Official Title
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Phase I Study of Specific CAR-T Dual-targeting HER2 and PD-L1 in Patients With Pleural or Peritoneal Metastasis of HER2 Positive Cancer

Conditions
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Peritoneal Carcinoma Metastatic, Pleural Effusion, Malignant

Intervention / Treatment
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* Biological: Dual-targeting HER2 and PD-L1 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, Age 18-65 years old; Estimated life expectancy ≥ 3 months (according to investigator's judgement); The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2; 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; Expressing HER2 >20% of primary tumors or metastatic cells in the serous cavity by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH); Absolute neutrophil count ≥ 1×10^9/L, platelet count ≥ 75×10^9/L, absolute lymphocyte count ≥1×10^8/L, hemoglobin ≥ 9.0 g/dl; Creatinine clearance rate ≥60ml/min, Serum ALT/AST≤2.5 times of the normal level, and total bilirubin≤1.5 times of the normal level; Cardiac ejection fraction ≥50%, no pericardial effusion; No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy); Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment; 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; Voluntarily participate in the research, understand and sign the informed consent; The side effect of the last anti-tumor treatment was reduced to ≤1 grade, except for hair loss. Exclusion Criteria: Allergic to cytokines; Uncontrolled activity infection; Acute or chronic (graft-versus-host disease) GVHD; Accompanied by other uncontrolled malignant tumors; Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level; Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.; Patients with grade 2-3 hypertension or poorly controlled; History of mental illness that is difficult to control; Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy; 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; Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy; Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T cell therapy<br>Dual-targeting HER2 and PD-L1 CAR-T cell therapy | Biological: Dual-targeting HER2 and PD-L1 CAR-T cells<br>* serosal cavity infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Related Adverse Events | AE during the first 28 days after CAR-T cell administration | 12 months | 
| Dose-limiting toxicity (DLT) | Baseline up to 28 days after CAR-T cells infusion | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR（objective response rate） | Include CR（complete response）and PR（partial response） | Month 1，month 3, month 6 | 
| DOR (duration of response) | The time from achievement of disease control | 12 months |