safety and preliminary efficacy of anti-cdh17 car-t cell therapy in patients with cdh17-positive advanced solid tumors

Conditions: CDH17-positive Advanced Solid Tumors

Summary: this is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-cdh17 car-t cells in patients with cdh17-positive advanced solid tumors.

this is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-cdh17 car-t cells in patients with cdh17-positive advanced solid tumors.a leukapheresis procedure will be performed to manufacture anti-cdh17 chimeric antigen receptor (car) modified t cells. prior to anti-cdh17 car-t cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. after infusion, the safety and efficacy of car-t therapy was evaluated by investigators.

Eligibility criteria:
inclusion criteria: 1. the patient understands and voluntarily signs the informed consent form, and is expected to complete the follow-up examination and treatment of the study procedures; 2. age 18-75 years old, gender unlimited; 3. tumor patients who have positive expression of cdh17 target in tumor tissues measured by immunohistochemistry (ihc) in a laboratory approved by the partner, and have no standard therapy or are ineffective or not suitable for standard treatment; 4. have at least one extracranial measurable lesion according to recist 1.1 criteria; 5. estimated survival ≥ 12 weeks; 6. baseline ecog (eastern cooperative oncology group) score ≤ 1 point; 7. the patient has recovered from the toxicity of the prior treatment, i.e., ctcae toxicity grade \< 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy); 8. venous access could be established; without contraindications of apheresis. exclusion criteria: 1. patients with prior or current other malignancies; 2. presence of brain metastases and clinically significant central nervous system disease; 3. prior antitumor therapy (prior to blood collection for car-t preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter; 4. subjects with positive hbsag or hbcab positive and peripheral blood hbv dna titer is higher than the lower limit of detection of the research institution; hcv antibody positive; hiv antibody positive; cmv dna titer is higher than the lower limit of detection of the research institution; ebv dna titer is higher than the lower limit of detection of the research institution 5. those who have a positive sputum smear and t-cell test for tuberculosis infection; 6. patients with objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function, both past and present; 7. patients have a severe allergic history; 8. patients with severe heart disease or uncontrollable refractory hypertension; 9. patients with severe liver and kidney dysfunction or consciousness disorders; 10. active autoimmune or inflammatory diseases of the nervous system; 11. uncontrolled infections that need antibiotics treatment; 12. live attenuated vaccine within 4 weeks before screening; 13. alcoholics or persons with a history of drug abuse; 14. pregnant or lactating women; patients and his or her spouse have a fertility plan within two years after car-t cell infusion; 15. any unsuitable to participate in this trial judged by the investigator.

Keywords: cdh17 car-t