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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: CT041 autologous CAR T-cell injection; Drug: Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）

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.

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Guangzhou
    • Shenzhen, Guangzhou, China
      • Peking University Shenzhen Hospital
  • Heilongjia
    • Harbin, Heilongjia, China
      • Harbin Medical University Affiliated Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China
      • Henan Tumor Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
    • Suzhou, Jiangsu, China
      • The Second Affiliated Hospital of Soochow University
    • Yangzhou, Jiangsu, China
      • Northern Jiangsu People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • The Second Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China
      • Shanghai Zhongshan Hospital
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China
      • Sichuan Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Hanzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT041 autologous CAR T-cell injection; Two stages: Phase 1b: dose escalation and dose expansion; Phase 2: verify CT041 efficacy and safety	Drug: CT041 autologous CAR T-cell injection; Up to 3 times CT041 autologous CAR T-cell injection infusion; Other Names: CAR T-cell injection
Active Comparator: Physician's Choice; Participants will receive physician's choice of treatment in Phase II	Drug: Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）; Physician's choice of any BSC listed above; Other Names: Best support care(BSC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Incidence of Treatment Related adverse events (AEs)	Incidence of treatment related AEs, AEs of special interest and serious adverse events(SAEs).	Up to 18 months
Phase Ib: Identification of Maximum Tolerated Dose (MTD)	Incidence of dose-limiting toxicities (DLTs)	day1-day28
Phase II: Progression-free survival (PFS), as assessed by IRC, of CT041 autologous CAR T-cell injection versus Physician's Choice	Progression-free survival (PFS) was defined as the time from the date of randomization to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib: Objective Response Rate (ORR), as assessed by Investigators	The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.	Up to 18 months
Phase Ib: Progression-free survival (PFS), as assessed by Investigators	Progression-free survival (PFS) was defined as the time from the date of first infusion of CT041 to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.	Up to 18 months
Phase Ib：Overall survival (OS)	Overall Survival (OS) was defined as the time from the date of first infusion of CT041 to the date of death due to any cause.	Up to 18 months
Phase Ib：Duration of response (DOR), as assessed by Investigators	Duration of response (DOR) is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death.	Up to 18 months
Phase Ib：Disease control rate (DCR), as assessed by Investigators	Disease control rate (DCR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1.	Up to 18 months
Phase II: Overall survival (OS) of CT041 autologous CAR T-cell injection versus Physician's Choice	Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.	Up to 24 months
Progression-free survival (PFS), as assessed by Investigators, of CT041 autologous CAR T-cell injection versus Physician's Choice	Progression-free survival (PFS) was defined as the time from the date of randomization to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.infusion	Up to 24 months
Phase II：Objective Response Rate (ORR), as assessed by IRC and by Investigators	The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.	Up to 24 months
Phase II: Duration of response (DOR), as assessed by IRC and by Investigators	Duration of response (DOR) is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death.	Up to 24 months
Phase II: Disease control rate (DCR), as assessed by IRC and by Investigators	Disease control rate (DCR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1.	Up to 24 months

Collaborators and Investigators

• Sponsor: CARsgen Therapeutics Co., Ltd.
• Collaborators: Fudan University; Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Xianjun Yu, Professor, Fudan University; Principal Investigator: Lin Shen, Professor, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Actual): October 18, 2024
• Study Completion (Estimated): June 30, 2038

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Estimated): June 5, 2025
• Last Update Submitted That Met QC Criteria: June 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CAR T cell; Gastric Cancer; Pancreatic Cancer; advanced solid tumors; Claudin18.2; Esophagogastric Junction Cancer; CLDN18.2
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Pancreatic Neoplasms; Adenocarcinoma; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Irinotecan; Antibodies; Paclitaxel; Apatinib
• Other Study ID Numbers: CT041-ST-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No