Phase 1/2 Study of Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer
This is a multicenter, open-label Phase 1/2 clinical trial evaluating the safety and preliminary efficacy of sequentially administered CD146-targeted and GPC3-targeted CAR-T cell therapy in patients with advanced relapsed or refractory ovarian cancer. Eligible patients will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by an infusion of autologous CD146-directed CAR-T cells (Arm A) and a subsequent infusion of autologous GPC3-directed CAR-T cells (Arm B). The Phase 1 portion will assess safety, tolerability, and dose-limiting toxicities (DLTs) to determine a recommended Phase 2 dose, while the Phase 2 portion will evaluate efficacy endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients will be followed for up to 36 months after CAR-T infusion to monitor long-term outcomes and adverse events.
• Expected survival time ≥3 months;
• Diagnosis: Histologically or cytologically confirmed epithelial ovarian carcinoma (including fallopian tube or primary peritoneal carcinoma considered as ovarian cancer) that is relapsed or refractory to standard therapies. Patients must have received and progressed on or after at least one line of platinum-based chemotherapy (or be platinum-resistant) and have no curative standard treatment options.
• Target Antigen Expression: Tumor must demonstrate positive expression of CD146 and GPC3 by immunohistochemistry (IHC) on a recent tumor tissue sample. Expression of both targets is required for eligibility (to ensure the presence of the CAR-T targets in the patient's cancer).
• Disease Status: Measurable disease as defined by RECIST 1.1 criteria (at least one measurable lesion on imaging).
• Age: Adults aged ≥18 years. (Patients must be legally adult and able to provide informed consent. Upper age limit may not be specified, but patients must meet other health criteria.)
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (indicative of fully active or restricted in physically strenuous activity only).
• Organ Function: Adequate organ and bone marrow function, including: absolute neutrophil count (ANC) above a minimum threshold, platelet count above threshold, hemoglobin above threshold (transfusion allowed), serum AST/ALT and bilirubin ≤2× upper limit of normal (unless due to liver involvement by tumor), and adequate renal function (e.g. creatinine clearance ≥50 mL/min or per protocol criteria).
• Consent: Ability to understand and sign informed consent, and willing to comply with trial procedures and follow-up. Women of child-bearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for a defined period after CAR-T cell infusion (due to unknown risks to a fetus).