Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Pancreatic Cancer
Conditions
Keywords
Claudin18.2, CAR-T cell therapy
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.
Interventions
DRUGCT048 Autologous Injection (CT048)
up to 3 times CT048 Autologous Injection infusion
Sponsors
CARsgen Therapeutics Co., Ltd.
Peking University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | 28 days of single infusion | Safety |
| Maximum tolerated dose | 28 days of single infusion | Tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antitumor efficacy-Overall response rate (ORR), Duration of response (DOR), Disease control rate (DCR) | 1 year | 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) | 1 year | The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause |
| Nature, incidence, severity and seriousness of TEAEs, TRAEs and AESI; graded according to the NCI-CTCAE (Version 5.0) or ASTCT | 1 year | 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. |
| Antitumor efficacy-Progression-free survival | 1 year | 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) | 2 years | 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). |
| Antitumor efficacy-Disease control rate (DCR) | 1 year | The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%). |
| Pharmacokinetics(the number of CAR copies and CAR persistence duration in peripheral blood) | 1 year | CAR-CLDN18.2 DNA in peripheral blood detected by q-PCR at each visit after each infusion |
Countries
China
Contacts
Primary Contactlin Shen, MD,phD
Backup ContactChangsong Qi, MD, PhD
Outcome results
None listed