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

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

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

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: CT048 Autologous Injection (CT048)

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.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: lin Shen, MD,phD; Phone Number: 861088196561; Email: linshenpku@163.com
• Study Contact Backup: Name: Changsong Qi, MD, PhD; Phone Number: 861088196561; Email: xiwangpku@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital, Beijing, China
    • Contact: Lin Shen, MD; Phone Number: 008688196561; Email: shenlin@bjmu.edu.cn
    • Contact: Yanshuo Cao, MD; Phone Number: 008688196561; Email: yanshuo.cao@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: CT048 Autologous Injection (CT048); up to 3 times CT048 Autologous Injection infusion; Other Names: CT048 Autologous CAR T-cell Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Safety	28 days of single infusion
Maximum tolerated dose	Tolerability	28 days of single infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumor efficacy-Duration of response (DOR)	The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause	1 year
Antitumor efficacy-Disease control rate (DCR)	The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).	1 year
Nature, incidence, severity and seriousness of TEAEs, TRAEs and AESI; graded according to the NCI-CTCAE (Version 5.0) or ASTCT	Adverse events occurring through 24 weeks and 12 months post CT048 indusion, such as abnormalities or changes in laboratory tests, physical examinations, vital signs, etc.	1 year
Pharmacokinetics(the number of CAR copies and CAR persistence duration in peripheral blood)	CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after each infusion	1 year
Antitumor efficacy-Overall response rate (ORR), Duration of response (DOR), Disease control rate (DCR)	The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 6 weeks after the first evaluation	1 year
Antitumor efficacy-Progression-free survival	The period from the date of leukapheresis to the first recorded tumor progression or death of any cause, whichever occurs first (ITT).	1 year
Antitumor efficacy-Overall survival (OS)	The period from the date of leukapheresis to death of any cause (ITT). The period from the date of first CT048 infusion to death of any cause (mITT).	2 years

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: CARsgen Therapeutics Co., Ltd.
• Investigators: Principal Investigator: Lin Shen, MD,phD, Department of GI Oncology, Peking University Cancer Hospita

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Estimated): June 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: May 13, 2022
• First Submitted That Met QC Criteria: May 24, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: CAR-T cell therapy; Claudin18.2
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma
• Other Study ID Numbers: CT048-CG4001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No