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

Pleural Effusion, Malignant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04684459
• Other study ID #: MCART-002
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 12, 2021
• Est. completion date: December 30, 2025

Study information

• Verified date: November 2023
• Source: Sichuan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male or female, Age 18-65 years old;

2. Estimated life expectancy = 3 months (according to investigator's judgement);

3. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-2;

4. 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;

5. Expressing HER2 >20% of primary tumors or metastatic cells in the serous cavity by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH);

6. 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;

7. 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;

8. Cardiac ejection fraction =50%, no pericardial effusion;

9. No other serious diseases (autoimmune diseases or any immune deficiency disease or other disease in need of immunosuppressive therapy);

10. Patients must stop chemotherapy and targeted therapy for at least 3 weeks before starting treatment;

11. 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;

12. Voluntarily participate in the research, understand and sign the informed consent;

13. The side effect of the last anti-tumor treatment was reduced to =1 grade, except for hair loss.

Exclusion Criteria:

1. Allergic to cytokines;

2. 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. Suffer from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, etc.;

7. Patients with grade 2-3 hypertension or poorly controlled;

8. History of mental illness that is difficult to control;

9. Patients have used immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroid therapy;

10. 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;

11. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment. If receiving anticoagulant therapy;

12. Pregnant or nursing women, or plan to become pregnant during the treatment period or within 1 year after the treatment ends;

13. 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.

Related Conditions & MeSH terms

• Peritoneal Carcinoma Metastatic
• Pleural Effusion
• Pleural Effusion, Malignant

Intervention

Biological:
• Dual-targeting HER2 and PD-L1 CAR-T cells
serosal cavity infusion

Locations

Country	Name	City	State
China	West China Hospital, Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Related Adverse Events	AE during the first 28 days after CAR-T cell administration	12 months
Primary	Dose-limiting toxicity (DLT)	Baseline up to 28 days after CAR-T cells infusion	12 months
Secondary	ORR(objective response rate)	Include CR(complete response)and PR(partial response)	Month 1,month 3, month 6
Secondary	DOR (duration of response)	The time from achievement of disease control	12 months