Injection of Anti-CDH17 CAR-T cells for advanced solid tumors

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

This study is testing if injections of a new type of immune cell treatment can help people with advanced solid tumors that have a specific marker called CDH17.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai Pudong Hospital (other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, cyclophosphamide, fludarabine, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06501183 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and preliminary efficacy of Anti-CDH17 CAR-T cell injections in patients with advanced malignant solid tumors that express CDH17. It consists of two phases: a dose escalation phase to determine the maximum tolerated dose and a dose expansion phase to further assess safety and efficacy. All participants will undergo a conditioning chemotherapy regimen before receiving the CAR-T cell injection. The study aims to provide insights into the potential of this innovative treatment for difficult-to-treat cancers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with CDH17-positive advanced malignant solid tumors that have not responded to standard therapies.

Not a fit: Patients with tumors that do not express CDH17 or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced solid tumors that are currently difficult to treat.

How similar studies have performed: While CAR-T cell therapies have shown success in hematological malignancies, this approach targeting solid tumors is still largely novel and untested.

Eligibility criteria

Inclusion Criteria:

1. 18 to 70 years old (including cut-off value), gender is not limited.
2. 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.
3. At least one measurable lesion according to RECIST v1.1.
4. CDH17 should be positive confirmed by Immunohistochemistry/Immunocytochemistry (IHC/ICC) in tumor tissue samples.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy ≥ 3 months.
7. Organ function must meet protocol requirements
8. 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.
9. 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:

1. 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.
2. Pregnant or lactating women.
3. 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.
4. 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.
5. 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.)
6. Patients have received anti-CDH17 CAR-T cell therapy.
7. 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.
8. 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.
9. 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;
   * Acute coronary syndrome (such as: unstable angina, myocardial infarction) within 6 months prior to signing informed consent;
   * Drug-uncontrolled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg) or pulmonary hypertension;
   * Cerebrovascular accident occurred within 6 months prior to signing informed consent, including transient ischemic attack (TIA), cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage;
   * A history of active, chronic, or recurrent (within 1 year prior to signing informed consent) severe autoimmune disease or immune-mediated disease requiring steroids or other immunosuppressive therapy, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis. Exceptions: hypothyroidism that can be controlled only by hormone replacement therapy, skin diseases (such as: vitiligo, psoriasis) that do not require systemic treatment, coeliac disease that has been controlled;
   * Any form of primary or secondary immunodeficiency, such as severe combined immunodeficiency (SCID);
   * Possibility of bleeding from esophageal or gastric varices evaluated by the investigator.
10. History of severe systemic hypersensitivity reaction to the drugs/ingredients \[fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular dextran, human serum albumin (HSA), etc.\] used in this study.
11. Patients have received attenuated vaccine within 4 weeks prior to signing informed consent.
12. Patients have received other clinical trials within 4 weeks prior to signing informed consent.
13. History of another malignancy tumor within the previous five years, except for adequately treated non-melanoma skin cancer, carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
14. History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator, including but not limited to epilepsy, schizophrenia, dementia, drug and alcohol addictions.
15. For any other reasons, the patients are believed not suitable for participation in this study by investigators.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Pudong hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Zhiguo Long

Conditions: CDH17-positive Advanced Malignant Solid Tumors