Sequential CD146 and GPC3 CAR-T therapy for advanced ovarian cancer
Phase 1/2 Study of Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer
This trial will try two sequential CAR-T cell infusions—first targeting CD146 then GPC3—in adults with advanced ovarian cancer that has returned or not responded to standard treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 21 Years to 90 Years |
| Sex | All |
| Sponsor | Essen Biotech Academic / other |
| Drugs / interventions | CAR-T, chemotherapy, cyclophosphamide, fludarabine, CAR T, immunotherapy |
| Locations | 1 site (Beijing, Beijing Municipality) |
| Trial ID | NCT07067255 on ClinicalTrials.gov |
What this trial studies
This multicenter, open-label Phase 1/2 trial gives lymphodepleting cyclophosphamide and fludarabine followed by autologous CD146-directed CAR-T cells and, after a short interval, autologous GPC3-directed CAR-T cells. Phase 1 uses dose-escalation to define safety, tolerability and a recommended Phase 2 dose, and Phase 2 will measure objective response rate, progression-free survival, and overall survival. Eligible patients must have measurable relapsed or refractory epithelial ovarian cancer with positive CD146 and GPC3 expression on recent tumor tissue. Patients will be followed for up to 36 months to monitor responses and long-term adverse events.
Who should consider this trial
Good fit: Adults with relapsed or refractory epithelial ovarian cancer who have progressed after at least one line of platinum-based chemotherapy, have measurable disease, an expected survival of at least three months, and tumor expression of both CD146 and GPC3 are eligible.
Not a fit: Patients whose tumors do not express both CD146 and GPC3, who have rapidly progressive disease, poor performance status, or alternative curative options are unlikely to benefit from this trial.
Why it matters
Potential benefit: If effective, the dual-target approach could produce broader tumor killing and extend progression-free and overall survival for some patients with relapsed or refractory ovarian cancer.
How similar studies have performed: CAR-T therapies have achieved major success in blood cancers but have shown only limited early activity in solid tumors; GPC3-directed CAR-Ts have reported preliminary responses in small studies while CD146 targeting and sequential dual-CAR approaches remain largely experimental.
Eligibility criteria
Show full inclusion / exclusion 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).
Where this trial is running
Beijing, Beijing Municipality
- District One Hospital — Beijing, Beijing Municipality, China (Recruiting)
Study contacts
- Study coordinator: Rhoda M Smith, Phd
- Email: clinical-trials@essen-biotech.com
- Phone: +12077706670
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.