Evaluating CT041 CAR T-cell therapy for advanced gastric and pancreatic cancers

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

This study is testing a new CAR T-cell therapy to see if it can help people with advanced gastric or pancreatic cancer whose previous treatments haven't worked.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: CARsgen Therapeutics Co., Ltd. (Industry-sponsored)
• Drugs / interventions: CAR-T, immunotherapy, CAR T, chimeric antigen receptor
• Locations: 24 sites (Hefei, Anhui and 23 other locations)
• Trial ID: NCT04581473 on ClinicalTrials.gov

What this trial studies

This open, multicenter Phase Ib/II clinical trial assesses the efficacy, safety, and pharmacokinetics of CT041 autologous CAR T-cell injections in patients with advanced gastric/esophagogastric junction adenocarcinoma and pancreatic cancer. The study targets patients whose tumors express Claudin18.2 and who have previously failed multiple lines of therapy. The trial consists of a dose escalation and expansion phase followed by a verification phase to confirm treatment efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced gastric or pancreatic cancer who have failed prior treatments and have tumors expressing Claudin18.2.

Not a fit: Patients with tumors that do not express Claudin18.2 or those who have not failed the required number of prior therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced gastric and pancreatic cancers that have limited treatment alternatives.

How similar studies have performed: Other studies utilizing CAR T-cell therapies have shown promising results, indicating potential success for this novel approach in treating advanced solid tumors.

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.

Where this trial is running

Hefei, Anhui and 23 other locations

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

Study contacts

• Principal investigator: Lin Shen, Professor — Peking University Cancer Hospital & Institute
• Study coordinator: Lifeng Zhang, MD

Conditions Gastric Adenocarcinoma; Pancreatic Cancer; Gastroesophageal Junction Adenocarcinoma; advanced solid tumors; Gastric Cancer; Esophagogastric Junction Cancer; Claudin18.2; CLDN18.2