Clinical trial NCT04581473: Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection
Official title: 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric Adenocarcinoma
Pancreatic Cancer
Gastroesophageal Junction Adenocarcinoma
Keywords: advanced solid tumors
Gastric Cancer
Pancreatic Cancer
Esophagogastric Junction Cancer
Claudin18.2
CLDN18.2
CAR T cell
Lead sponsor: CARsgen Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University Cancer Hospital & Institute
name: Fudan University
First posted: 2020-10-09
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase Ib: Incidence of Treatment Related adverse events (AEs)
timeFrame: Up to 18 months
measure: Phase Ib: Identification of Maximum Tolerated Dose (MTD)
timeFrame: day1-day28
measure: Phase II: Progression-free survival (PFS), as assessed by IRC, of CT041 autologous CAR T-cell injection versus Physician's Choice
timeFrame: Up to 24 months
Secondary outcomes:
measure: Phase Ib: Objective Response Rate (ORR), as assessed by Investigators
timeFrame: Up to 18 months
measure: Phase Ib: Progression-free survival (PFS), as assessed by Investigators
timeFrame: Up to 18 months
measure: Phase Ib：Overall survival (OS)
timeFrame: Up to 18 months
measure: Phase Ib：Duration of response (DOR), as assessed by Investigators
timeFrame: Up to 18 months
measure: Phase Ib：Disease control rate (DCR), as assessed by Investigators
timeFrame: Up to 18 months
measure: Phase II: Overall survival (OS) of CT041 autologous CAR T-cell injection versus Physician's Choice
timeFrame: Up to 24 months
measure: Progression-free survival (PFS), as assessed by Investigators, of CT041 autologous CAR T-cell injection versus Physician's Choice
timeFrame: Up to 24 months
measure: Phase II：Objective Response Rate (ORR), as assessed by IRC and by Investigators
timeFrame: Up to 24 months
measure: Phase II: Duration of response (DOR), as assessed by IRC and by Investigators
timeFrame: Up to 24 months
measure: Phase II: Disease control rate (DCR), as assessed by IRC and by Investigators
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
state: Guangzhou
city: Harbin
country: China
facility: Harbin medical university Affiliated Cancer Hospital
state: Heilongjia
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hanzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Xianjun Yu, Professor
role: PRINCIPAL_INVESTIGATOR
References: