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

NCT06084286 | Recruiting Phase 1

• 1 other identifier: MCART-007
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Keywords

CAR-T cell therapy; Solid Tumors; CLDN18.2-positive

Outcome Measures

Primary Outcomes (3)

• Adverse Events (AEs)

  Safety evaluation. AEs will be recorded and evaluated by CTCAE 5.0.

  28 days

• Dose-limiting toxicity (DLT)

  Tolerability evaluation. DLT will be assessed by CTCAE 5.0.

  28 days

• Recommended phase II dose (RP2D)

  Efficacy dose.

  Approximately 18 months

Secondary Outcomes (8)

• Objective Remission Rate (ORR)

  3 months

• Progression-Free Survival (PFS)

  Approximately 18 months

• Duration of Control Rate (DCR)

  Approximately 18 months

• Duration of Response (DOR)

  Approximately 18 months

• Overall-Survival (OS)

  Approximately 18 months

Study Arms (1)

CAR-T cell therapy

EXPERIMENTAL

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

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

Interventions

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

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

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;
• 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;
• Must have CLDN18.2-positive tumor expression ≥10% as determined by the CLDN18.2 IHC assay;
• Estimated life expectancy \> 3 months (according to investigator's judgement);
• At least 1 measurable lesion per RECIST 1.1;
• The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
• Patients should have reasonable CBC counts, renal and hepatic functions;
• No other serious diseases (autoimmune diseases or any immune deficiency disease);
• 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;
• 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;
• Voluntarily participate in the research, understand and sign the informed consent.

You may not qualify if:

• Pregnant or lactating women;
• Patient with hepatitis B or C active period, HIV infection ≥ the upper limit of the normal level;
• Any uncontrolled active infection;
• Patients who have clinically significant thyroid dysfunction;
• Patients who have received prior cellular therapy such as CAR T, TCR, tumor-infiltrating lymphocytes;
• Patients who are allergic to immunotherapy or any associated drugs, such as cytokines and the preconditioning regimen (cyclophosphamide, fludarabine);
• Patients with untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
• Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
• Unstable pulmonary embolism, deep venous embolism or other major arterial/venous thromboembolic events occurred within 6 months before enrollment;
• Patients with active autoimmune diseases, history of autoimmune diseases or other diseases in need of immunosuppressive therapy;
• Patients with major surgery or injury less than 4 weeks prior to leukapheresis or plan to have major surgery during the research period;
• Patients with second malignancies in addition to targeted malignancies within 5 years before screening;
• Patients with unstable/active ulcer or digestive tract bleeding;
• 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;
• Patients who have a history or a tendency for digestive tract bleeding;

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 23559882 BACKGROUND

• 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.

  PMID: 33633361 BACKGROUND

Study Officials

• YongShen Wang, Prof.

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yao Zeng

CONTACT

(+86)15982172735; yao_zeng@stu.scu.edu.cn

Dan Li, PhD.

CONTACT

(+86)13880025826; lidan@wchscu.cn

Study Design

• Study Type: interventional
• Phase: 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: October 3, 2023
• First Posted: October 16, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)