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

Sponsor

CARsgen Therapeutics Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04581473

Collaborator

Peking University Cancer Hospital & Institute (Other), Fudan University (Other)

192

Enrollment

Locations

Arms

212.2

Anticipated Duration (Months)

19.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma Pancreatic Cancer Gastroesophageal Junction Adenocarcinoma	Drug: CT041 autologous CAR T-cell injection Drug: Physician's Choice（Paclitaxel or Irinotecan or Apatinib or Anti-PD-1 antibody）	Phase 1/Phase 2

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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

192 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 23, 2020

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2038

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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 Ib: Identification of Maximum Tolerated Dose (MTD) [day1-day28]
Incidence of dose-limiting toxicities (DLTs)
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

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 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：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 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.
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.
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
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: 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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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;
Aged 18 to 75 years;
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;
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;
Estimated life expectancy >12 weeks;
According to the RECIST 1.1, there is measurable tumor lesions;
ECOG physical status score 0 ~ 1 at screening, within 24 hours prior to apheresis, and at baseline;
Sufficient venous access for mononuclear cell collection;
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;
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;
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:

Pregnant or lactating women;
HIV, Treponema pallidum or HCV serologically positive;
Any uncontrollable active infection, including but not limited to active tuberculosis, HBV infection;
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;
Patients known to have active autoimmune diseases, including but not limited to psoriasis or rheumatoid arthritis, or other diseases requiring long-term immunosuppressive therapy;
Previously allergic to immunotherapy and related drugs,history of severe allergies, or allergic to components of CT041.
Previously received any gene-modified cell therapies(including CAR-T, TCR-T);
Patients have brain metastasis or symptoms of brain metastasis;
Patients at high risk of hemorrhage or perforation;
Patients requiring anticoagulant therapy;
Patients requiring continuous anti-platelet therapy;
Patients with a history of organ transplantation or awaiting organ transplantation;
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;
Presence of other serious pre-existing medical conditions that may limit patient participation in the study;
The investigator assessed that the patient was unable or unwilling to comply with the requirements of the study protocol;
Prior to pretreatment, patients developed, including but not limited to, new arrhythmias that could not be controlled with drugs, hypotension requiring pressor agent, bacterial, fungal or viral infections that required intravenous antibiotics. The investigator judges that the patient is not suitable for continuing the trial. Patients who use antibiotics to prevent infection can continue the trials if judged by the investigator;
The patient has a central nervous system disease sign or an abnormal neurological test result with clinical significance;
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anhui Provincial Cancer Hospital	Hefei	Anhui	China
2	Beijing Cancer Hospital	Beijing	Beijing	China	100142
3	Harbin medical university Affiliated Cancer Hospital	Harbin	Heilongjia	China
4	Henan Tumor Hospital	Zhengzhou	Henan	China
5	Nanjing Drum Tower Hospital	Nanjing	Jiangsu	China
6	Ruijin Hospital, affiliated to Shanghai Jiaotong University, school of medicine	Shanghai	Shanghai	China	200025
7	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
8	Shanghai Zhongshan Hospital	Shanghai	Shanghai	China
9	West China Hospital, Sichuan University	Chengdu	Sichuan	China
10	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China	300060

Sponsors and Collaborators

CARsgen Therapeutics Co., Ltd.
Peking University Cancer Hospital & Institute
Fudan University

Investigators

Principal Investigator: Lin Shen, Professor, Peking University Cancer Hospital & Institute
Principal Investigator: Xianjun Yu, Professor, Fudan University