Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer

Launched by ESSEN BIOTECH · Jul 5, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment approach for people with advanced ovarian cancer that has come back or not responded to standard treatments. The treatment uses special immune cells called CAR-T cells, which are made from a patient’s own blood cells and then modified in the lab to better recognize and attack cancer cells. In this study, patients will receive two types of these CAR-T cells, one targeting a protein called CD146 and another targeting a protein called GPC3, given one after the other. Before receiving the CAR-T cells, patients will have chemotherapy to help prepare their body to accept the treatment. The main goals are to see if this treatment is safe and to get an early look at how well it works against the cancer.

To join the trial, patients must be adults with ovarian cancer that has returned or not improved after standard chemotherapy, and their tumors need to have both CD146 and GPC3 proteins present. They should be in good overall health, able to perform daily activities, and expected to live at least three more months. Patients with certain other health problems, active brain cancer spread, or previous CAR-T treatments targeting these proteins are not eligible. During the trial, participants will be closely monitored for side effects and cancer response, with follow-up visits for up to three years to track long-term outcomes. This study is currently recruiting patients at multiple centers.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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).
• Exclusion Criteria:
• • Prior Therapy: Previous treatment with any CAR-T cell therapy or other gene-engineered T-cell therapy targeting CD146 or GPC3. (Patients who received prior immunotherapies such as checkpoint inhibitors are allowed if a washout period is met, but prior CAR-T could confound results or pose increased risk.)
• • CNS Involvement: Active central nervous system (CNS) metastases or carcinomatous meningitis. (Patients with a history of CNS metastases that have been effectively treated and are radiographically stable off steroids may be eligible, per protocol specifics.)
• • Comorbid Illness: Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, clinically significant heart failure (e.g. NYHA Class III-IV), unstable angina or arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. (Patients with controlled chronic conditions may be eligible at the investigator's discretion.)
• • Immunosuppression: Active hepatitis B or C infection with viremia, or known HIV infection with uncontrolled viral load. Patients requiring chronic systemic immunosuppressive therapy (e.g. for an autoimmune condition or organ transplant) are excluded, except for physiologic dose steroids.
• • Pregnancy or Breastfeeding: Pregnant or breastfeeding women are excluded due to potential risks to the fetus or infant from the study treatment. Women of child-bearing potential who are unwilling or unable to use adequate contraception are not eligible.
• • Other Malignancy: Presence of another active malignancy requiring treatment (with the exception of certain early-stage cancers or those in remission for a specified period, per protocol). This is to avoid confounding outcomes and ensure patient safety.
• • Hypersensitivity: Known severe hypersensitivity to any component of the investigational CAR-T cell products or to the lymphodepletion chemotherapy drugs (cyclophosphamide, fludarabine).
• • Other Exclusions: Any condition that, in the opinion of the investigator, would make the patient unsuitable for the study (such as life expectancy limited by comorbid illness, or significant laboratory abnormalities not covered above).