Clinical trial NCT06820424: Safety and Preliminary Efficacy of Anti-CDH17 CAR-T Cell Therapy in Patients with CDH17-positive Advanced Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety and Preliminary Efficacy of CDH17 CAR-T in Patients with CDH17-positive Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: CDH17-positive Advanced Solid Tumors
Keywords: CDH17 CAR-T
Lead sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Sponsor class: OTHER
Collaborators: name: Guangzhou Bio-gene Technology Co., Ltd
First posted: 2025-02-11
Enrollment: 30
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: 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.

Detailed description: 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.

Primary outcomes:
measure: Incidence of adverse events(AE) after infusion
timeFrame: within 52 weeks post-infusion
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: within 52 weeks post-infusion
measure: Concentration of CAR-T cells
timeFrame: Days 2, 5, 8, 11, 14, 21, 28, 35 and weeks 6, 12, 18, 26, 34, 42, 52 after infusion
measure: Progression-free survival(PFS)
timeFrame: within 52 weeks post-infusion
measure: Overall survival(OS)
timeFrame: within 52 weeks post-infusion
Other outcomes:
Locations:
city: Kunming
country: China
facility: Sanbin Wang
state: Yunnan
Study officials:
affiliation: Principal Investigator Sanbin Wang 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: