Clinical trial NCT05393986: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Gastric Adenocarcinoma
Pancreatic Cancer
Gastroesophageal Junction Adenocarcinoma
Keywords: Claudin18.2
CAR-T cell therapy
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: CARsgen Therapeutics Co., Ltd.
First posted: 2022-05-27
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 28 days of single infusion
measure: Maximum tolerated dose
timeFrame: 28 days of single infusion
Secondary outcomes:
measure: Nature, incidence, severity and seriousness of TEAEs, TRAEs and AESI; graded according to the NCI-CTCAE (Version 5.0) or ASTCT
timeFrame: 1 year
measure: Pharmacokinetics(the number of CAR copies and CAR persistence duration in peripheral blood)
timeFrame: 1 year
measure: Antitumor efficacy-Overall response rate (ORR), Duration of response (DOR), Disease control rate (DCR)
timeFrame: 1 year
measure: Antitumor efficacy-Duration of response (DOR)
timeFrame: 1 year
measure: Antitumor efficacy-Disease control rate (DCR)
timeFrame: 1 year
measure: Antitumor efficacy-Progression-free survival
timeFrame: 1 year
measure: Antitumor efficacy-Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital, Beijing, China
Study officials:
affiliation: Department of GI Oncology, Peking University Cancer Hospita
name: Lin Shen, MD,phD
role: PRINCIPAL_INVESTIGATOR
References: