Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection

NCT ID: NCT04581473

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-23
• Study Completion Date: 2038-06-30

Brief Summary

An open, multicenter, phase Ib/II study to evaluate the efficacy, safety and pharmacokinetics of CT041 autologous CAR T-cell injection in patients with advanced gastric/ gastroesophageal junction adenocarcinoma and pancreatic cancer

Detailed Description

This study is an open, multicenter, Phase Ib/II clinical trial evaluating chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041 autologous CAR T) in subjects with CLDN18.2 expression-positive, advanced gastric/esophagogastric conjugate adenocarcinoma that has failed at least 2 prior lines therapy and advanced pancreatic cancer that has failed at least 1 prior line therapy. The purpose is to evaluate the efficacy, safety and pharmacokinetics There are two stages in the study. Phase Ib stage is dose escalation and dose expansion study, and Phase II stage is to verify the efficacy and safety of CT041 treatment.

Conditions

Gastric Adenocarcinoma; Pancreatic Cancer; Gastroesophageal Junction Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CT041 autologous CAR T-cell injection

Two stages: Phase 1b: dose escalation and dose expansion; Phase 2: verify CT041 efficacy and safety

Group Type: EXPERIMENTAL

CT041 autologous CAR T-cell injection

Intervention Type: DRUG

Up to 3 times CT041 autologous CAR T-cell injection infusion

Physician's Choice

Participants will receive physician's choice of treatment in Phase II

Group Type: ACTIVE_COMPARATOR

Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）

Intervention Type: DRUG

Physician's choice of any BSC listed above

Interventions

CT041 autologous CAR T-cell injection

Up to 3 times CT041 autologous CAR T-cell injection infusion

Intervention Type: DRUG

Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）

Physician's choice of any BSC listed above

Intervention Type: DRUG

Other Intervention Names

CAR T-cell injection; Best support care(BSC)

Eligibility Criteria

Inclusion Criteria

1. Be willing to participate in a clinical trial, be informed and sign inform consent; and be willing to follow and be able to complete all trial procedures;

2. Aged 18 to 75 years;

3. Phase Ib：Patients with pathologically diagnosed advanced gastric/ gastroesophageal junction adenocarcinoma who have failed at least 2 prior lines treatment; or patients with pathologically diagnosed advanced pancreatic cancer who have failed at least 1 prior line treatment ; Phase II：Patients with pathologically diagnosed advanced gastric/ gastroesophageal junction adenocarcinoma who have failed at least 2 prior lines treatment;

4. Phase Ib：Tumor tissue samples were positive for CLDN18.2 IHC staining； Phase II：Tumor tissue samples were positive for CLDN18.2 IHC staining and HER2 expression was negative;

5. Estimated life expectancy >12 weeks;

6. According to the RECIST 1.1, there is measurable tumor lesions;

7. ECOG physical status score 0 ~ 1 at screening, within 24 hours prior to apheresis, and at baseline;

8. Sufficient venous access for mononuclear cell collection;

9. Unless otherwise specified, patients should meet the certain conditions prior to screening and pre-treatment and be allowed one week to retest if an abnormal laboratory test does not meet the criteria, and if the criteria are still not met, the screening is considered to have failed;

10. Female patients of childbearing age must undergo a serum pregnancy test at screening and prior to pretreatment 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;

11. Men who have actively sexual intercourse with women with child-bearing potential, must agree to use barrier-based contraception if they have no vasectomy.

Exclusion Criteria

1. Pregnant or lactating women;

2. HIV, Treponema pallidum, HCV serologically positive, EBV-DNA, CMV-DNA or 2019-ncov nucleic acid positive;

3. Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection;

4. The side effects caused by the previous treatment of the subjects did not return to CTCAE ≤1; except hair loss and other tolerable events determined by investigator;

5. Patients known to have active autoimmune diseases, including but not limited to psoriasis or rheumatoid arthritis, or other diseases requiring long-term immunosuppressive therapy;

6. Previously allergic to immunotherapy and related drugs,history of severe allergies, or allergic to components of CT041.

7. Previously received any gene-modified cell therapies(including CAR-T, TCR-T);

8. Patients have brain metastasis or symptoms of brain metastasis;

9. Patients at high risk of hemorrhage or perforation;

10. Patients requiring anticoagulant therapy;

11. Patients requiring continuous anti-platelet therapy;

12. Patients with a history of organ transplantation or awaiting organ transplantation;

13. Patients who have undergone major surgery or significant trauma within 4 weeks prior to apheresis, or who are expected to undergo major surgery during the study;

14. Presence of other serious pre-existing medical conditions that may limit patient participation in the study;

15. The investigator assessed that the patient was unable or unwilling to comply with the requirements of the study protocol;

16. The patient has a central nervous system disease sign or an abnormal neurological test result with clinical significance;

17. The patient is currently suffered from or have suffered from other incurable malignant tumors within previous 3 years, except in situ cervical cancer or skin basal cell cancer.

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

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Fudan University

OTHER

Sponsor Role: collaborator

CARsgen Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lin Shen, Professor

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Xianjun Yu, Professor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Peking University Shenzhen Hospital

Shenzhen, Guangzhou, China

Harbin medical university Affiliated Cancer Hospital

Harbin, Heilongjia, China

Henan Tumor Hospital

Zhengzhou, Henan, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, China

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

The Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, China

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

The First Hospital of Jilin University

Changchun, Jilin, China

The First Hospital of China Medical University

Shenyang, Liaoning, China

Shandong Cancer Hospital

Jinan, Shandong, China

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine

Shanghai, Shanghai Municipality, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Shanghai Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Sichuan Cancer Hospital

Chengdu, Sichuan, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hanzhou, Zhejiang, China

Countries

China

References

Qi C, Liu C, Peng Z, Zhang Y, Wei J, Qiu W, Zhang X, Pan H, Niu Z, Qiu M, Qin Y, Fang W, Ye F, Li N, Liu T, Liu A, Zhang X, Hu C, Zhang J, Cui J, Lin X, Wang S, Zhang J, Lin T, Qu X, Yuan X, Gong J, Li J, Gao W, Gai L, Wang Y, Yuan D, Li Z, Shen L. Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial. Lancet. 2025 Jun 7;405(10494):2049-2060. doi: 10.1016/S0140-6736(25)00860-8. Epub 2025 May 31.

Reference Type: DERIVED

PMID: 40460847 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38788174 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37689733 (View on PubMed)

Other Identifiers

CT041-ST-01

Identifier Type: -

Identifier Source: org_study_id