Dual-targeting HER2 and PD-L1 CAR-T for Solid Tumors

NCT04684459 | Recruiting Early Phase 1

• 1 other identifier: MCART-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

CAR-T therapy has achieved unprecedented success in hematological tumors in recent years, but the progress of CAR-T cells in the treatment of solid tumors is facing difficulties. HER-2 is frequently expressed in breast cancer, ovarian cancer, lung cancer, gastric cancer and other malignant tumors. In this study, the PD-L1 inhibitory signal was transformed into an activation signal in the tumor microenvironment, and enhanced the killing activity and survival ability of CAR-T cells. The HER-2/PD-L1 dual-targeting CAR-T will be investigated in patients with HER2-positive solid tumors, and all enrolled subjects will receive HER2/PD-L1 CAR T cells via intravenous or thoracic/peritoneal cavity infusion.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• ORR（objective response rate）

  Month 1，month 3, month 6

• DOR (duration of response)

  12 months

Study Arms (1)

CAR-T cell therapy

EXPERIMENTAL

Dual-targeting HER2 and PD-L1 CAR-T cell therapy

Biological: Dual-targeting HER2 and PD-L1 CAR-T cells

Interventions

Dual-targeting HER2 and PD-L1 CAR-T cells BIOLOGICAL

HER2-positive solid tumor serosal cavity infusion

CAR-T cell therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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, 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;
• 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 ≥0.5×10\^8/L, hemoglobin ≥ 8.0 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (1)

• Ma Q, He X, Zhang B, Guo F, Ou X, Yang Q, Shu P, Chen Y, Li K, Gao G, Zhu Y, Qin D, Tang J, Li X, Jing M, Zhao J, Mo Z, Liu N, Zeng Y, Zhou K, Feng M, Liao W, Lei W, Li Q, Li D, Wang Y. A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis. Signal Transduct Target Ther. 2022 Nov 19;7(1):380. doi: 10.1038/s41392-022-01198-2.

  PMID: 36402752 DERIVED

MeSH Terms

Conditions

Pleural Effusion, Malignant

Condition Hierarchy (Ancestors)

Pleural Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Pleural Effusion; Pleural Diseases; Respiratory Tract Diseases

Central Study Contacts

Qizhi Ma, Dr

CONTACT

+8602885421139; maqzh95@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Institute of Drug Clinical Trial of West China Hospital

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: March 12, 2021
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: October 30, 2024

Record last verified: 2024-10

Locations

CN (1)