claudin18.2-redirected chimeric antigen receptor t cells with co-expression of cytokines in solid tumors

Conditions: Gastric Adenocarcinoma; Pancreatic Cancer; Gastroesophageal Junction Adenocarcinoma

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

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;

Keywords: claudin18.2 car-t cell therapy