Claudin18.2-redirected Chimeric Antigen Receptor T Cells With Co-expression of Cytokines in Solid Tumors

NCT ID: NCT05393986

Last Updated: 2023-05-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-04
• Study Completion Date: 2024-12-30

Brief Summary

An Open-Label, Single-Arm, Dose-Exploration Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetics of CT048 in Subjects with Advanced Solid Tumors

Detailed Description

This is an open-label, single-arm, dose-escalation and dose-expansion, single/multiple infusion(s) exploratory study to evaluate the safety, tolerability, PK/PD and preliminary efficacy of CT048 in patients with advanced CLDN18.2+ solid tumors who had failed to at least 1 prior line of treatment.

Conditions

Gastric Adenocarcinoma; Pancreatic Cancer; Gastroesophageal Junction Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: CAR-CLDN18.2 T-Cells (CT048)

The subjects will be initially enrolled in the lymphodepletion cohort. Subsequent subjects will be enrolled in the non-lymphodepletion cohort after reviewing the data in the lymphodepletion cohort.

Group Type: EXPERIMENTAL

CT048 Autologous Injection (CT048)

Intervention Type: DRUG

up to 3 times CT048 Autologous Injection infusion

Interventions

CT048 Autologous Injection (CT048)

up to 3 times CT048 Autologous Injection infusion

Intervention Type: DRUG

Other Intervention Names

CT048 Autologous CAR T-cell Injection

Eligibility Criteria

Inclusion Criteria

1. Aged 18 to 75 years, male or female;

2. Estimated life expectancy > 12 weeks;

3. Pathologically/histologically confirmed diagnosis of advanced G/GEJ adenocarcinoma or pancreatic cancer or other digestive system malignancies G/GEJA: refractory to or intolerable of at least 2 prior lines of treatment; HER2+ subjects must be refractory or intolerable of anti-HER2 treatment PC: refractory to or intolerable of at least 1 prior line of treatment;

4. Positive expression of CLDN18.2 in tumor tissue specimens;

5. According to the RECIST 1.1, there is measurable or unmeasurable tumor lesions;

6. ECOG physical status score 0 ~ 1 at screening, within 24 hours prior to apheresis;

7. Sufficient venous access for leukapheresis (central venous catheter)

8. Subjects should have adequate organ functions before screening :

9. Women of childbearing age (WOCB) be willing to use effective and reliable method of contraception (annual failure<1%) for at least 1 year after last infusion, and must refrain from donating sperms/eggs

10. Men who have actively sexual intercourse with women with child-bearing potential, must agree to use barrier-based contraception if they have no vasectomy. Moreover, all men are absolutely forbidden to donate sperm within 1 year after receiving the last infusion.

Exclusion Criteria

1. High risks that may cause bleeding or perforation;

2. CNS metastasis, with or without related symptoms;

3. The presence of extensive lung metastases, or extensive liver metastases, or extensive bone metastases

4. History or current unstable or active digestive ulcers, gastrointestinal (GI) bleeding, GI obstruction;

5. Anti-tumor treatment for the investigational disease; treatment with anti-PD-1/PD-L1, anti-CTLA4, and any other immunotherapy or investigational therapy；

6. Prior treatment with any genetically modified cell therapy;

7. Treatment with systemic corticosteroids within 7 days prior to leukapheresis;

8. Prior solid organ transplantation, or allogeneic stem cell, or in the waiting list for organ transplantation;

9. Major surgical procedure or serious wound within 4 weeks prior to leukapheresis, or anticipation of need for a major surgical procedure during the study;

10. Positive serological tests of HIV, syphilis or HCV (subjects with positive HCV antibody but are negative for HCV RNA are eligible);

11. Any active or severe infection, incl. but not limited to active tuberculosis, HBV infection, etc.;

12. Active autoimmune disease;

13. Uncontrolled significant cardiovascular disease, pulmonary disease or CNS disease

14. History of malignancy other than investigational diseases within 3 years, with the exception of malignancies with a negligible risk of metastasis or death;

15. Pregnancy or lactating women;

16. History of allergic anaphylactic reactions to immunotherapy, and/or tocilizumab, cyclophosphamide, fludarabine or nab-paclitaxel, and/or CT048 components, or other history of severe allergic anaphylactic reactions ；

17. Blood oxygen saturation ≤95% before leukapheresis;

18. AEs from previous treatment that have not recovered to CTCAE ≤ grade 1, excluding hair loss, pigmentation, and other tolerable events and laboratory abnormalities permitted by the protocol;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CARsgen Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lin Shen, MD,phD

Role: PRINCIPAL_INVESTIGATOR

Department of GI Oncology, Peking University Cancer Hospita

Locations

Beijing Cancer Hospital, Beijing, China

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

lin Shen, MD,phD

Role: CONTACT

linshenpku@163.com

861088196561

Changsong Qi, MD, PhD

Role: CONTACT

xiwangpku@126.com

861088196561

Facility Contacts

Lin Shen, MD

Role: primary

shenlin@bjmu.edu.cn

008688196561

Yanshuo Cao, MD

Role: backup

yanshuo.cao@bjmu.edu.cn

008688196561

Other Identifiers

CT048-CG4001

Identifier Type: -

Identifier Source: org_study_id