Zimberelimab Plus Metformin for Recurrent Ovarian Clear Cell Carcinoma

Study Overview
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Brief Summary
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This study aims to evaluate the safety and effectiveness of zimberelimab combined with metformin in treating relapsed/persistent ovarian clear cell carcinoma.

Detailed Description
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Ovarian clear cell carcinoma (OCCC) is one of the rare subtypes of ovarian cancer, yet its prognosis is extremely poor. Previous studies indicate that PD-1 inhibitors may have clinical benefits for OCCC patients. This single-arm, single-center, pilot study evaluates the safety and effectiveness of zimberelimab combined with metformin in treating relapsed/persistent ovarian clear cell carcinoma.

Official Title
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Zimberelimab Combined With Metformin in the Treatment of Recurrent Ovarian Clear Cell Carcinoma: A Pilot Study

Conditions
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Ovarian Clear Cell Carcinoma

Intervention / Treatment
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* Drug: Zimberelimab
* Drug: Metformin Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years to ≤ 75 years Pathologic confirmed ovarian clear cell carcinoma Patients with recurrent or persistent ovarian clear cell carcinoma must have at least one-line pretreated platinum-containing chemotherapy According to the definition of RECIST1.1, the patient must have measurable lesions PD-L1 Combined Positive Score ≥ 1 ECOG performance status of 0 to 2 Adequate bone marrow, liver, and renal function to receive combined immunotherapy Written informed consent Exclusion Criteria: Histological evidence of non-ovarian clear cell carcinoma Lack of tumor samples (archived and/or recently obtained) Previous administration of immunotherapy Patients have been vaccinated with the live vaccine or received anti-tumor treatment within 4 weeks before the first administration An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) within 2 years before the first administration Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ or breast cancer (without any signs of relapse or activity) Symptomatic or uncontrolled visceral metastases that require simultaneous treatment Patients are known to be allergic to the active ingredients or excipients of zimberelimab or metformin Known human immunodeficiency virus (HIV) infection history (HIV 1/2 antibody positive). Untreated active hepatitis B (defined as HBsAg positive and the number of copies of HBV-DNA detected at the same time is greater than the upper limit of the normal value of the laboratory department of the research center) Contraindications to metformin: kidney dysfunction or abnormal creatinine from any cause; acute or metabolic acidosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: zimberelimab plus metformin<br>Patients will start metformin at 1,000mg by mouth once daily during a 7-day induction period prior to starting zimberelimab. The dose will be increased by 500mg every 7 days until reaching the target dose of 2000mg. Zimberelimab will be administered at a fixed dose of 240 mg IV every 14 days. Treatment will continue until disease progression confirmed by RECIST criteria v1.1, intolerable toxicity, or withdrawal of consent. | Drug: Zimberelimab<br>* Zimberelimab 240mg IV every 2 weeks<br>* Other names: Anti PD-1;Drug: Metformin Hydrochloride<br>* Metformin 2000mg PO QD<br>* Other names: Metformin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The proportion of patients with complete response (CR) and partial response (PR) assessed by the investigator in accordance with the RECIST 1.1 criteria | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first | Up to 2 years | 
| Overall survival | The time from date of randomization until the date of death from any cause or last follow-up | Up to 2 years | 
| Disease control rate | The proportion of patients who achieved complete response (CR) or partial response (PR) or stable disease (SD) assessed by the investigator in accordance with the RECIST 1.1 criteria | Up to 2 years | 
| Duration of response | The time interval from the first record of disease response to disease progression or death (whichever occurs first) | Up to 2 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | The adverse event assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Up to 2 years | 
| Patterns of subsequent recurrence | The number and sites of subsequent recurrence, including pelvic, abdominal, retroperitoneal lymph nodes, hepato-celiac lymph nodes and distant metastases and ascites, etc.) | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Clear Cell Carcinoma, Immune Checkpoint Inhibitor, Metformin