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

Phase 1

Recruiting

• Conditions: Gastric Adenocarcinoma; Pancreatic Cancer; Gastroesophageal Junction Adenocarcinoma
• Interventions: Drug: Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）; Drug: CT041 autologous CAR T-cell injection

• Registration Number: NCT04581473
• Lead Sponsor: CARsgen Therapeutics Co., Ltd.

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.

Study Timeline

• Study First Submitted: 2020-09-24
• Study First Submitted QC: 2020-10-05
• Study First Posted: 2020-10-09
• Study Start: 2020-10-23
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06
• Primary Completion: 2024-06-30
• Study Completion: 2038-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 192

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Physician's Choice	Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）	Participants will receive physician's choice of treatment in Phase II
CT041 autologous CAR T-cell injection	CT041 autologous CAR T-cell injection	Two stages: Phase 1b: dose escalation and dose expansion; Phase 2: verify CT041 efficacy and safety

Primary Outcome Measures

Name	Time	Method
Phase Ib: Identification of Maximum Tolerated Dose (MTD)	day1-day28	Incidence of dose-limiting toxicities (DLTs)
Phase Ib: Incidence of Treatment Related adverse events (AEs)	Up to 18 months	Incidence of treatment related AEs, AEs of special interest and serious adverse events(SAEs).
Phase II: Progression-free survival (PFS), as assessed by IRC, of CT041 autologous CAR T-cell injection versus Physician's Choice	Up to 24 months	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.

Secondary Outcome Measures

Name	Time	Method
Phase Ib: Objective Response Rate (ORR), as assessed by Investigators	Up to 18 months	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.
Phase II: Overall survival (OS) of CT041 autologous CAR T-cell injection versus Physician's Choice	Up to 24 months	Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause.
Phase Ib：Overall survival (OS)	Up to 18 months	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.
Phase Ib：Duration of response (DOR), as assessed by Investigators	Up to 18 months	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.
Phase II：Objective Response Rate (ORR), as assessed by IRC and by Investigators	Up to 24 months	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.
Phase II: Disease control rate (DCR), as assessed by IRC and by Investigators	Up to 24 months	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.
Phase II: Duration of response (DOR), as assessed by IRC and by Investigators	Up to 24 months	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.
Phase Ib: Progression-free survival (PFS), as assessed by Investigators	Up to 18 months	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.
Phase Ib：Disease control rate (DCR), as assessed by Investigators	Up to 18 months	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.
Progression-free survival (PFS), as assessed by Investigators, of CT041 autologous CAR T-cell injection versus Physician's Choice	Up to 24 months	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

Trial Locations

Locations (24)

The Affiliated Hospital of Qingdao University; 🇨🇳 Qingdao, Shandong, China

Anhui Provincial Cancer Hospital; 🇨🇳 Hefei, Anhui, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, 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

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology; 🇨🇳 Wuhan, Hubei, China

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Henan Tumor Hospital; 🇨🇳 Zhengzhou, Henan, China

Nanjing Drum Tower Hospital; 🇨🇳 Nanjing, Jiangsu, China

Northern Jiangsu People's Hospital; 🇨🇳 Yangzhou, Jiangsu, China

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China

The Second Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine; 🇨🇳 Shanghai, Shanghai, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

The First Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

The Second Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Shanghai Zhongshan Hospital; 🇨🇳 Shanghai, Shanghai, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, 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