Anti-CDH17 CAR-T Cell Injection in Patients With CDH17-positive Advanced Malignant Solid Tumors

NCT06501183 | Recruiting Phase 1

• 1 other identifier: Anti-CDH17 CAR-T cells
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

CDH17-positive Advanced Malignant Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Adverse Events (AEs)

  Incidence and severity of adverse events.

  2 years

• Serious Adverse Events (SAEs)

  Incidence and severity of serious adverse events.

  2 years

• Adverse Events of Special Interest (AESI)

  Incidence and severity of adverse event of special interest.

  2 years

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

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

  4 weeks after the CAR-T cells infusion

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Bio-distribution of CAR-T cells

  2 years

Study Arms (1)

Anti-CDH17 CAR-T cells

EXPERIMENTAL

Anti-CDH17 CAR-T cells

Biological: Anti-CDH17 CAR-T cells

Interventions

Anti-CDH17 CAR-T cells BIOLOGICAL

Anti-CDH17 CAR-T cell injection will be administered intravenously after lymphodepleting.

Anti-CDH17 CAR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1.
• CDH17 should be positive confirmed by Immunohistochemistry/Immunocytochemistry (IHC/ICC) in tumor tissue samples.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.

You may not qualify if:

• 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.);
• Lung disease requiring systemic hormone therapy;
• Congestive heart failure with New York Heart Association (NYHA) functional class \> 1;
• Clinically significant severe aortic stenosis and symptomatic mitral stenosis;
• Electrocardiogram QTc \> 450 msec or QTc \> 480 msec in patients with bundle-branch block;
• Uncontrolled clinically significant arrhythmia within 6 months prior to signing informed consent;

Sponsors & Collaborators

• Shanghai Pudong Hospital: lead
• UTC Therapeutics Inc.: collaborator

Study Sites (1)

Shanghai Pudong hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Central Study Contacts

Zhiguo Long

CONTACT

18117253161; zglong1976@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Model Details: Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 15, 2024
• Study Start: July 8, 2024
• Primary Completion: May 30, 2025
• Study Completion (Estimated): May 30, 2026
• Last Updated: July 15, 2024

Record last verified: 2024-07

Locations

CN (1)