CAR-T cell therapy for advanced gynecological tumors

A Phase I Clinical Trial of MUC1-targeted CAR-T Cells with PD1 Nanobody MSLN Dual-target for Advanced Gynecological Solid Tumors

This study is testing if CAR-T cell therapy can help people with advanced gynecological tumors by seeing how safe it is and how well it works.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Obstetrics & Gynecology Hospital of Fudan University (other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy, cyclophosphamide
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06904131 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of CAR-T cell therapy in patients with advanced gynecological solid tumors. Participants undergo a conditioning regimen followed by the reinfusion of engineered T cells, with a focus on determining the maximum tolerated dose through a dose-escalation approach. The study includes monitoring for adverse events and assessing clinical efficacy based on disease response. Follow-up evaluations will occur regularly to track patient outcomes and the pharmacokinetics of the CAR-T cells.

Who should consider this trial

Good fit: Ideal candidates are females aged 18 to 70 with advanced gynecological solid tumors that express specific biomarkers and have failed standard treatments.

Not a fit: Patients with early-stage gynecological tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced gynecological tumors who have exhausted standard therapies.

How similar studies have performed: While CAR-T cell therapy has shown promise in other cancers, this specific application for gynecological solid tumors is relatively novel and untested.

Eligibility criteria

inclusion criteria

1. Patients with gynecological solid tumors diagnosed by histopathology, with tumor tissue sample MUC1 expression rate ≥50% or MSLN expression rate ≥50%, PD-L1 positive expression, and sample source within 2 years;
2. Patients with advanced gynecological solid tumors who have failed standard treatment or are intolerant to such treatment and have no standard effective treatment options;
3. Females aged 18 to 70 years (inclusive);
4. Estimated survival time ≥ 3 months;
5. ECOG performance status score of 0 to 1 at screening and baseline;
6. Good organ and bone marrow function:

   1. The researcher assesses sufficient bone marrow function to receive lymphocyte-depleting chemotherapy: Neutrophil count ≥1.5 × 10\^9/L, lymphocyte count ≥0.5 × 10\^9/L;
   2. Platelet count ≥90 × 10\^9/L;
   3. Hemoglobin ≥90 g/L (no blood transfusion or no erythropoietin-dependent within 7 days);
   4. Total bilirubin ≤2 times the upper limit of normal value;
   5. Serum creatinine ≤1.5 times the upper limit of normal value;
   6. Transaminase (AST, ALT) ≤2.5 times the upper limit of normal value (if liver metastasis is present, 5 times the upper limit of normal value);
   7. International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 times the upper limit of normal value;
   8. Pulmonary function: ≤ CTCAE grade 1 dyspnea and SaO2 ≥ 91% in room air;
   9. Cardiac function: Echocardiogram or radionuclide ventriculography (MUGA) assessment left ventricular ejection fraction (LVEF) ≥50% within 1 month of enrollment.

exclusion criteria

1. Participants who have undergone other anti-tumor treatments not allowed by the protocol within 1 month before CAR-T infusion (including radiotherapy, chemotherapy, small molecules, biological treatment, or immunotherapy, other research drugs);
2. Participants who have previously received targeted therapy against MUC1 or MSLN, or cellular therapy, or any gene therapy products (including CAR-T cell therapy) or any T cell therapy at home or abroad;
3. Pregnant or breastfeeding women;
4. AIDS virus, syphilis seroreactivity positive; hepatitis B surface antigen positive, or hepatitis B core antibody positive and hepatitis B virus DNA copies higher than the detection limit or greater than or equal to 1000 copies/mL; or hepatitis C virus infection;
5. Any uncontrollable active infection, coagulopathy, or any other major disease;
6. Patients with active autoimmune diseases being treated, organ transplantation and other immune-related diseases, or long-term use of immunosuppressive drugs such as glucocorticoids: a. Glucocorticoids cannot be discontinued within 72 hours before CAR-T cell infusion; b. Immunosuppressive agents other than glucocorticoids cannot be discontinued ≥4 weeks before enrollment;
7. Patients with severe cardiopulmonary insufficiency, uncontrolled hypertension, any of the following cardiovascular disease histories within the past 6 months: III or IV heart failure defined by the New York Heart Association (NYHA), cardiac catheterization or stent, myocardial infarction, unstable angina, or other clinically significant heart disease;
8. Patients with confirmed brain metastasis, or those with a history of or current central nervous system disease, such as epileptic seizures, cerebrovascular ischemia/hemorrhage, dementia, encephalopathy, or any autoimmune disease associated with the central nervous system;
9. Patients with high risk of bleeding or perforation;
10. Patients who underwent major surgery or significant trauma within 4 weeks before single collection;
11. Patients with other malignant tumors within 3 years or concurrently (except for skin basal cell carcinoma, cervical/breast cancer in situ, etc.);
12. Any other conditions deemed unsuitable for participation in the study by the investigator.

Where this trial is running

Shanghai, Shanghai Municipality

• The Obstetrics and Gynecology Hospital of Fudan University — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Xin Wu

Conditions: Gynecological Solid Tumors