Chimeric Antigen Receptor T Cells Targeting claudin18.2 in Solid Tumors.

NCT03874897 | Completed Phase 1 DMC

• 1 other identifier: CT041-CG4006
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 3

Brief Summary

An open label, single/multiple dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor T cell in advanced solid tumor.

Conditions

Advanced Solid Tumor

Keywords

Advanced solid tumor; claudin18.2; CAR-T cell therapy

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Safety

  28 days of single infusion

• Maximum tolerated dose (MTD)

  tolerability

  28 days of single infusion

Secondary Outcomes (9)

• Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood)

  26 weeks

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  1 year

• Antitumor efficacy-Progression-free survival (PFS)

  1 year

• Antitumor efficacy-Duration of response (DOR)

  1 year

• Antitumor efficacy-Duration of disease control (DDC)

  1 year

Study Arms (5)

CAR-CLDN18.2 T-Cells

EXPERIMENTAL

The subjects enrolled will be sequentially assigned to the corresponding dose level.

Drug: CAR-CLDN18.2 T-Cells

Cohort 1

EXPERIMENTAL

CT041 monotherapy in patients with GI cancers who failed standard chemotherapy

Drug: CAR-CLDN18.2 T-Cells

Cohort 2

EXPERIMENTAL

CT041 plus anti-PD1 therapy in patients with GI cancers who failed standard chemotherapy

Drug: CAR-CLDN18.2 T-Cells; Drug: PD-1 Monoclonal Antibody

Cohort 3

EXPERIMENTAL

CT041 sequential treatment after first-line therapy in GC/GEJ

Drug: CAR-CLDN18.2 T-Cells; Drug: Chemotherapy

Cohort 4

EXPERIMENTAL

prior treatment failure to anti-CLDN18.2 monoclonal antibody

Drug: CAR-CLDN18.2 T-Cells

Interventions

CAR-CLDN18.2 T-Cells DRUG

Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses • Chimeric Antigen Receptor T Cells Targeting Claudin18.2

Also known as: Chimeric Antigen Receptor T Cells Targeting Claudin18.2

CAR-CLDN18.2 T-Cells; Cohort 1; Cohort 2; Cohort 3; Cohort 4

PD-1 Monoclonal Antibody DRUG

Chimeric Antigen Receptor T Cells Targeting Claudin18.2 with PD-1

Also known as: Toripalimab

Cohort 2

Chemotherapy DRUG

First-line systemic therapy according to physician's choice

Cohort 3

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 75 years, male or female;
• Subjects with pathologically confirmed solid tumors (ie, advanced gastric cancer, esophagogastricgastroesophageal junction cancer, and pancreatic cancer) and have been failed to at least first-one prior line of systemic treatment;
• Tumor tissue samplessample was positive for claudin 18.2 positive through for claudin18.2 IHC staining;assay(≥2+, and ≥40%);
• Estimated life expectancy \> 12 weeks;
• According to the RECIST 1.1, there is at least one measurable or unmeasurable tumor lesionslesion；
• ECOG physical status score 0 \~ 1, within 24 hours prior to apheresis, and at baseline (prior to pre-treatment);
• Sufficient venous access for mononuclear cell collection (abbreviation: apheresis)
• Subjects should have adequate organ functions before screening and pre-treatment (at baseline).
• Female subjects of childbearing age must undergo a serum pregnancy test at screening and prior to preconditioning and the results must be negative, and are willing to use a very effective and reliable method of contraception within 1 year after the last study treatment. The methods that can be used are: bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusion; or approved oral, injection or hormone-imparting contraceptive methods; or barrier contraceptive method: containing spermicidal foam / Gel/film/cream/suppository condom or occlusive cap (diaphragm or cervix/cap);
• Subject participates in this clinical trial and sign Informed Consent Form voluntarily.

You may not qualify if:

• Pregnant or lactating women;
• HIV, Treponema pallidum or HCV serologically positive;
• Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection (HBsAg positive, or HBcAb positive and HBV DNA positive);
• Subjects have clinically significant thyroid dysfunction determined by investigator (serum thyroid hormone assays TT4, TT3, FT3, FT4, and serum thyroid stimulating hormone TSH) which is not suitable for entering into the study;
• The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and, hyperpigmentation or other tolerable events determined by investigator or laboratory abnormalities allowed by the protocol;
• Subjects who are using steroidshave recieved ≥15 mg/day glucocorticoid systemically currently within 7 days prior to apheresis; those using inhaled steroids recently or currently are not excluded;
• Previously allergic to immunotherapy and related drugs, history of severe allergiespreconditioning drug such as cyclophosphamide, fludarabine, or allergiestocilizumab or allergic to components of CT041CAR-CLDN18.2T injection, allergic to β-lactam antibiotics;the CT041 infusion;
• Previously received any chimeric antigen receptor-modified T-cells(including CAR-T、TCR-T) .
• Subjects have untreated or symptomatic brain metastases;
• Subjects have central or extensivelywith centralcor diffused metastases in lung and .extensiveor diffused metastases in liver;liveror with rapid tumor progression since screening period evaluated by the investigator preconditioning (at baseline)；
• The largest target tumor lesion\>4cm
• Subjects with unstable or active ulcers and gastrointestinal bleeding currently;
• Subjects with a history of organ transplantation or awaiting organ transplantation;
• Subjects requiring anticoagulant therapy;
• Subjects requiring continuous anti-platelet therapy;

Sponsors & Collaborators

• Peking University: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (3)

Department of GI Oncology, Peking University Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

The First Affiliated Hospital , Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

Location

Related Publications (6)

• Li J, Liu L, Tao M, Han Z, Ma M, Jiang L, Liu C, Liu D, Zhang P, Zhang M, Xue R, Gong J, Zhang X, Shen L, Qi C. Impact of concomitant medications on efficacy of CLDN18.2-specific CAR-T cell therapy in advanced gastric cancer. Br J Cancer. 2026 Feb;134(3):439-446. doi: 10.1038/s41416-025-03289-7. Epub 2025 Nov 29.

  PMID: 41318814 DERIVED

• Li J, Tao M, Liu L, Liu C, Ma M, Liu D, Zhang P, Zhang M, Xue R, Gong J, Zhang C, Zhang X, Shen L, Qi C. Peripheral blood neutrophils contribute to Claudin18.2-specific CAR-T cell treatment resistance in advanced gastric cancer. Br J Cancer. 2025 Jun;132(12):1167-1176. doi: 10.1038/s41416-025-03015-3. Epub 2025 Apr 17.

  PMID: 40246985 DERIVED

• Qi C, Liu C, Gong J, Liu D, Wang X, Zhang P, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Lu Z, Lu M, Cao Y, Yuan J, Wang Y, Wang Z, Xue R, Peng X, Wang Y, Yuan D, Li J, Zhang X, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med. 2024 Aug;30(8):2224-2234. doi: 10.1038/s41591-024-03037-z. Epub 2024 Jun 3.

  PMID: 38830992 DERIVED

• Qi C, Zhang P, Liu C, Zhang J, Zhou J, Yuan J, Liu D, Zhang M, Gong J, Wang X, Li J, Zhang X, Li N, Peng X, Liu Z, Yuan D, Baffa R, Wang Y, Shen L. Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials. J Clin Oncol. 2024 Jul 20;42(21):2565-2577. doi: 10.1200/JCO.23.02314. Epub 2024 May 24.

  PMID: 38788174 DERIVED

• Qi C, Xie T, Zhou J, Wang X, Gong J, Zhang X, Li J, Yuan J, Liu C, Shen L. CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer. J Hematol Oncol. 2023 Sep 9;16(1):102. doi: 10.1186/s13045-023-01491-9.

  PMID: 37689733 DERIVED

• Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Cao Y, Zhang X, Lu Z, Lu M, Yuan J, Wang Z, Wang Y, Peng X, Gao H, Liu Z, Wang H, Yuan D, Xiao J, Ma H, Wang W, Li Z, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022 Jun;28(6):1189-1198. doi: 10.1038/s41591-022-01800-8. Epub 2022 May 9.

  PMID: 35534566 DERIVED

MeSH Terms

Interventions

spartalizumab; toripalimab; Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Lin Shen

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 14, 2019
• Study Start: March 26, 2019
• Primary Completion: March 20, 2021
• Study Completion: January 26, 2024
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (3)