CAR-T therapy targeting HER2 and PD-L1 for solid tumors

Phase I Study of Specific CAR-T Dual-targeting HER2 and PD-L1 for HER2-positive Solid Tumors

This study is testing a new CAR-T therapy that targets two proteins to see if it can help people with certain types of cancer, like breast and lung cancer, feel better.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT04684459 on ClinicalTrials.gov

What this trial studies

This study investigates a novel CAR-T therapy that targets both HER2 and PD-L1 in patients with HER2-positive solid tumors. The approach aims to enhance the effectiveness of CAR-T cells by transforming the PD-L1 inhibitory signal into an activation signal within the tumor microenvironment. Participants will receive the dual-targeting CAR-T cells through intravenous or thoracic/peritoneal cavity infusion. The study focuses on patients with various types of cancers that express HER2, including breast, ovarian, and lung cancers.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with HER2-positive solid tumors who have not responded to standard treatments.

Not a fit: Patients with solid tumors that do not express HER2 or those who are not eligible for CAR-T therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve treatment outcomes for patients with HER2-positive solid tumors.

How similar studies have performed: While CAR-T therapies have shown success in hematological cancers, 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; If the subjects are over 75 years old, the researchers will determine whether to enroll according to the basic health conditions of the subjects, regardless of gender. No upper age limit was set for chest/abdominal reinfusion CAR-T subjects.
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, head and neck cancer, pancreatic cancer, colorectal cancer, transitional cell carcinoma, endometrial carcinoma, sarcoma, glioblastoma, cholangiocarcinoma, etc. have received standard systemic treatment, have systemic metastasis/serosal cavity metastasis or are not tolerated;
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 ≥0.5×10\^8/L, hemoglobin ≥ 8.0 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.

Where this trial is running

Chengdu, Sichuan

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

Study contacts

• Study coordinator: Qizhi Ma, Dr

Conditions Peritoneal Carcinoma Metastatic; Pleural Effusion, Malignant; HER2 Positive Malignancies