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
Trial ID: NCT05393986
Interventional - Phase 1 - Unknown status
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
Conditions
Gastric Adenocarcinoma
Pancreatic Cancer
Gastroesophageal Junction Adenocarcinoma
Interventions
CT048 Autologous Injection (CT048)
Eligibility
Inclusion 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
# 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;