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

Primary Purpose

Gastric Adenocarcinoma, Pancreatic Cancer, Gastroesophageal Junction Adenocarcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CT048 Autologous Injection (CT048)
Sponsored by
Peking University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Adenocarcinoma focused on measuring Claudin18.2, CAR-T cell therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Beijing Cancer Hospital, Beijing, ChinaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)
Safety
Maximum tolerated dose
Tolerability

Secondary Outcome Measures

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.
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
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
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
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 (%).
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).
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).

Full Information

First Posted
May 13, 2022
Last Updated
May 30, 2023
Sponsor
Peking University
Collaborators
CARsgen Therapeutics Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05393986
Brief Title
Claudin18.2-redirected Chimeric Antigen Receptor T Cells With Co-expression of Cytokines in Solid Tumors
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2022 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University
Collaborators
CARsgen Therapeutics Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Adenocarcinoma, Pancreatic Cancer, Gastroesophageal Junction Adenocarcinoma
Keywords
Claudin18.2, CAR-T cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: CAR-CLDN18.2 T-Cells (CT048)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CT048 Autologous Injection (CT048)
Other Intervention Name(s)
CT048 Autologous CAR T-cell Injection
Intervention Description
up to 3 times CT048 Autologous Injection infusion
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Safety
Time Frame
28 days of single infusion
Title
Maximum tolerated dose
Description
Tolerability
Time Frame
28 days of single infusion
Secondary Outcome Measure Information:
Title
Nature, incidence, severity and seriousness of TEAEs, TRAEs and AESI; graded according to the NCI-CTCAE (Version 5.0) or ASTCT
Description
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.
Time Frame
1 year
Title
Pharmacokinetics(the number of CAR copies and CAR persistence duration in peripheral blood)
Description
CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after each infusion
Time Frame
1 year
Title
Antitumor efficacy-Overall response rate (ORR), Duration of response (DOR), Disease control rate (DCR)
Description
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
Time Frame
1 year
Title
Antitumor efficacy-Duration of response (DOR)
Description
The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause
Time Frame
1 year
Title
Antitumor efficacy-Disease control rate (DCR)
Description
The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
Time Frame
1 year
Title
Antitumor efficacy-Progression-free survival
Description
The period from the date of leukapheresis to the first recorded tumor progression or death of any cause, whichever occurs first (ITT).
Time Frame
1 year
Title
Antitumor efficacy-Overall survival (OS)
Description
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).
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 to 75 years, male or female; Estimated life expectancy > 12 weeks; 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; Positive expression of CLDN18.2 in tumor tissue specimens; According to the RECIST 1.1, there is measurable or unmeasurable tumor lesions; ECOG physical status score 0 ~ 1 at screening, within 24 hours prior to apheresis; Sufficient venous access for leukapheresis (central venous catheter) Subjects should have adequate organ functions before screening : 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 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: High risks that may cause bleeding or perforation; CNS metastasis, with or without related symptoms; The presence of extensive lung metastases, or extensive liver metastases, or extensive bone metastases History or current unstable or active digestive ulcers, gastrointestinal (GI) bleeding, GI obstruction; Anti-tumor treatment for the investigational disease; treatment with anti-PD-1/PD-L1, anti-CTLA4, and any other immunotherapy or investigational therapy; Prior treatment with any genetically modified cell therapy; Treatment with systemic corticosteroids within 7 days prior to leukapheresis; Prior solid organ transplantation, or allogeneic stem cell, or in the waiting list for organ transplantation; Major surgical procedure or serious wound within 4 weeks prior to leukapheresis, or anticipation of need for a major surgical procedure during the study; Positive serological tests of HIV, syphilis or HCV (subjects with positive HCV antibody but are negative for HCV RNA are eligible); Any active or severe infection, incl. but not limited to active tuberculosis, HBV infection, etc.; Active autoimmune disease; Uncontrolled significant cardiovascular disease, pulmonary disease or CNS disease History of malignancy other than investigational diseases within 3 years, with the exception of malignancies with a negligible risk of metastasis or death; Pregnancy or lactating women; 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 ; Blood oxygen saturation ≤95% before leukapheresis; 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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
lin Shen, MD,phD
Phone
861088196561
Email
linshenpku@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Changsong Qi, MD, PhD
Phone
861088196561
Email
xiwangpku@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lin Shen, MD,phD
Organizational Affiliation
Department of GI Oncology, Peking University Cancer Hospita
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Cancer Hospital, Beijing, China
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lin Shen, MD
Phone
008688196561
Email
shenlin@bjmu.edu.cn
First Name & Middle Initial & Last Name & Degree
Yanshuo Cao, MD
Phone
008688196561
Email
yanshuo.cao@bjmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

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

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