Dual-targeting CLDN18.2 and PD-L1 CAR-T for Patients with CLDN18.2-positive Advanced Solid Tumors

NCT ID: NCT06084286

Last Updated: 2024-11-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2026-10-30

Brief Summary

Claudin18.2(CLDN18.2) is a kind of integrin membrane protein in the tight junction between epithelium and endothelium, which is highly expressed in many solid tumors, especially in gastric cancer and pancreatic cancer. The CLDN18.2/PD-L1 dual-targeting CAR-T will be investigated in patients with CLDN18.2-positive advance solid tumors.

Detailed Description

In this study, the CLDN18.2/PD-L1 dual-targeting CAR-T cells will be injected intravenously to patients with CLDN18.2-positive advanced solid tumors, such as gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and pancreatic adenocarcinoma, who had nearly no response to standard treatment. The safety and effectiveness will be evaluated. The safety evaluation standard refers to the standard of CTCAE 5.0. The evaluation standard of effectiveness refers to the evaluation standard of solid tumor curative effect RECIST 1.1 to evaluate the curative effect.

There are two phases of this study. The first is dose escalation phase, and 9 patients with CLDN18.2-positive advanced solid tumors are planned to be enrolled. The second is dose expansion phase. The curative effect has been observed in the first phase, and after the DLT observation period of the related dose group finished, the PI will decide whether to conduct the dose expansion research finally. It is planned to enroll 20 patients in dose expansion phase.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-T cell therapy

Dual-targeting CLDN18.2 and PD-L1 CAR-T cells

Group Type: EXPERIMENTAL

Dual-targeting CLDN18.2 and PD-L1 CAR-T cells

Intervention Type: BIOLOGICAL

The trial consists of a traditional '3 + 3' pattern dose-escalation phase and a dose-expansion phase.

Interventions

Dual-targeting CLDN18.2 and PD-L1 CAR-T cells

The trial consists of a traditional '3 + 3' pattern dose-escalation phase and a dose-expansion phase.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female, Age 18-75 years old;

2. Patients with pathologically/histologically confirmed diagnosis of solid tumors (such as advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and pancreatic adenocarcinoma) have received at least once systemic standard treatment and disease progressed; or refused/ cannot tolerate the subsequential standard treatment after the first line treatment;

3. Must have CLDN18.2-positive tumor expression ≥10% as determined by the CLDN18.2 IHC assay;

4. Estimated life expectancy > 3 months (according to investigator's judgement);

5. At least 1 measurable lesion per RECIST 1.1;

6. The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

7. Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;

8. Patients should have reasonable CBC counts, renal and hepatic functions;

9. No other serious diseases (autoimmune diseases or any immune deficiency disease);

10. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion;

11. Men must be willing to use effective and reliable method of contraception and are not allowed to donate sperm for at least 12-months after T-cell infusion;

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

Exclusion Criteria

1. Pregnant or lactating women;

2. Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;

3. Any uncontrolled active infection;

4. Patients who have clinically significant thyroid dysfunction;

5. Patients who have received prior cellular therapy such as CAR T, TCR, tumor-infiltrating lymphocytes;

6. Patients who are allergic to immunotherapy or any associated drugs, such as cytokines and the preconditioning regimen (cyclophosphamide, fludarabine);

7. Patients with untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;

8. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;

9. Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment;

10. Patients with active autoimmune diseases, history of autoimmune diseases or other diseases in need of immunosuppressive therapy;

11. Patients with major surgery or injury less than 4 weeks prior to leukapheresis or plan to have major surgery during the research period;

12. Patients with second malignancies in addition to targeted malignancies within 5 years before screening;

13. Patients with unstable/active ulcer or digestive tract bleeding;

14. Patient suffering from diseases that affect the signing of written informed consent or compliance with research procedures; or are unwilling or unable to comply with research requirements;

15. Patients who have a history or a tendency for digestive tract bleeding;

16. Patients who are inappropriate to participate in this research as considered by PI.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sichuan University

OTHER

Sponsor Role: lead

Responsible Party

Yongsheng Wang

Director of Institute of Drug Clinical Trial of West China Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YongShen Wang, Prof.

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yao Zeng

Role: CONTACT

yao_zeng@stu.scu.edu.cn

(+86)15982172735

Dan Li, PhD.

Role: CONTACT

lidan@wchscu.cn

(+86)13880025826

Facility Contacts

Yao Zeng

Role: primary

yao_zeng@stu.scu.edu.cn

(+86)15982172735

Dan Li, PhD

Role: backup

lidan@wchscu.cn

(+86)13880025826

YongShen Wang, Prof.

Role: backup

References

Cheema PK, Burkes RL. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer. Curr Oncol. 2013 Apr;20(2):e150-60. doi: 10.3747/co.20.1226.

Reference Type: BACKGROUND

PMID: 23559882 (View on PubMed)

Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, Ruella M, Savoldo B, Shah NN, Turtle CJ, Wayne AS, Abou-El-Enein M. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021 Jun;18(6):379-393. doi: 10.1038/s41571-021-00476-2. Epub 2021 Feb 25.

Reference Type: BACKGROUND

PMID: 33633361 (View on PubMed)

Other Identifiers

MCART-007

Identifier Type: -

Identifier Source: org_study_id