Exploratory Study to Evaluate the Safety and Preliminary Efficacy of Anti-CDH17 CAR-T Cell Injection in Patients With CDH17-positive Advanced Malignant Solid Tumors

Shanghai Pudong Hospital1 site in 1 country17 target enrollmentJuly 8, 2024

ConditionsCDH17-positive Advanced Malignant Solid Tumors

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: CDH17-positive Advanced Malignant Solid Tumors
Sponsor: Shanghai Pudong Hospital
Enrollment: 17
Locations: 1
Primary Endpoint: Adverse Events (AEs)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-arm, open-label, exploratory clinical study to evaluate the safety and preliminary efficacy of Anti-CDH17 CAR-T cell injection in patients with CDH17-positive advanced malignant solid tumors.

Detailed Description

This study will include two parts, dose escalation phase (accelerated titration and 3+3 design) followed by a dose expansion phase. All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by Anti-CDH17 CAR-T cell injection. The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-CDH17 CAR-T cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of Anti-CDH17 CAR-T cell injection, and establish recommended phase 2 dose (RP2D).

Registry

clinicaltrials.gov

Start Date

July 8, 2024

End Date

May 30, 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Pudong Hospital

Responsible Party

Principal Investigator

Minghua Yu, Dr

Chief physician

Shanghai Pudong Hospital

Eligibility Criteria

Inclusion Criteria

•18 to 70 years old (including cut-off value), gender is not limited.
•Solid tumors that histological diagnosis of malignancy refractory to, or relapsing after standard therapy, including but not limited to colorectal cancer, gastric cancer, pancreatic cancer, biliary tract cancer.
•At least one measurable lesion according to RECIST v1.
•CDH17 should be positive confirmed by Immunohistochemistry/Immunocytochemistry (IHC/ICC) in tumor tissue samples.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Life expectancy ≥ 3 months.
•Organ function must meet protocol requirements
•Female participants of childbearing potential must undergo a pregnancy test and the results must be negative. Female participants of childbearing potential or male participants whose sex partner has childbearing potential must be willing to use effective methods of contraception from screening period to at least 1 year after infusion.
•Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.

Exclusion Criteria

•Patients have received systemic therapy with cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior to signing informed consent; Patients have received systemic glucocorticoids (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive therapy within 2 weeks prior to signing informed consent; Patients have received systemic antitumor therapy with a biologic agent or other approved targeted small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to signing informed consent; Patients have received Chinese herbal medicine or Chinese patent medicine with anti-tumor indication within 1 week prior to signing informed consent.
•Pregnant or lactating women.
•Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in peripheral blood is higher than the lower limit of detection. Patients who is hepatitis C virus (HCV) antibody positive and quantification of HCV DNA in peripheral blood is higher than the lower limit of detection. Patients with human immunodeficiency virus (HIV) antibody positive, or syphilis antibody positive.
•The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to CTCAE, except for hair loss and peripheral sensory nerve disorders.
•Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
•Patients have received anti-CDH17 CAR-T cell therapy.
•Patients who have history of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent; or plan to have major surgery within 12 weeks of cell therapy.
•Presence of known central nervous system metastases, but the following patients will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic progression within 4 weeks before apheresis and return of any neurologic symptoms to baseline), and with no need for corticosteroids or other treatment for brain metastases for ≥ 4 weeks.
•Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patients' ability to tolerate the treatments used in this study or significantly increase the risk of complications.
•Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);

Outcomes

Primary Outcomes

Adverse Events (AEs)

Time Frame: 2 years

Incidence and severity of adverse events.

Serious Adverse Events (SAEs)

Time Frame: 2 years

Incidence and severity of serious adverse events.

Adverse Events of Special Interest (AESI)

Time Frame: 2 years

Incidence and severity of adverse event of special interest.

Identification of Maximum Tolerated Dose (MTD) & Incidence of Dose-limiting Toxicities (DLTs)

Time Frame: 4 weeks after the CAR-T cells infusion

Incidence and severity of dose-limiting toxicities (DLTs) following infusion of CAR-T cell injection, at each dose level tested in dose escalation phase.