89Zr-DFO-Mirvetuximab PET/CT Imaging for Companion Diagnosis and Response Evaluation in Ovarian Cancer

Early Phase 1Not Yet RecruitingNCT07790939

Peking University Cancer Hospital & Institute20 enrolled

Overview

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in women, with approximately 320,000 new cases and 200,000 deaths annually worldwide, and its incidence is rising. Current treatment mainly relies on surgery, chemotherapy, and radiotherapy, but EOC frequently develops platinum resistance and recurrence. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), was approved by the FDA in 2024 for FRα-positive, platinum-resistant EOC. However, it carries significant toxicities (ocular, interstitial lung disease, peripheral neuropathy) and a modest objective response rate of 33%, with rapid acquired resistance, underscoring the need for patient selection and response prediction via targeted imaging. FRα, a GPI-anchored cell-surface glycoprotein encoded by FOLR1, is minimally expressed in normal adult tissues but overexpressed in various epithelial tumors, including ovarian cancer. Its overexpression promotes invasion, metastasis, and potentially drug resistance, making it a promising theranostic target. While ¹⁸F-FDG PET/CT is widely used, it has limitations in detecting low-activity or small lesions and shows suboptimal sensitivity/specificity for nodal metastases. Radiolabeled folate probes (e.g., ⁹⁹ᵐTc-EC20) have demonstrated excellent FRα-targeting and clinical utility in selecting patients for FRα-directed therapies. Our team has developed ⁸⁹Zr-DFO-Mirvetuximab by conjugating the anti-FRα monoclonal antibody with the chelator p-isothiocyanatobenzyl-desferrioxamine B and radiolabeling with ⁸⁹Zr. Preclinically, this probe exhibited favorable stability, safety, and specific targeting of FRα-high tumors in xenograft models. Building on these results, we plan a clinical study enrolling 20 patients with newly diagnosed stage IV or first-recurrent EOC, who will undergo both ⁸⁹Zr-DFO-Mirvetuximab PET/CT and ¹⁸F-FDG PET/CT. The study aims to correlate radiotracer uptake with FRα expression and to demonstrate the superior performance of ⁸⁹Zr-DFO-Mirvetuximab in identifying and delineating ovarian cancer lesions compared to ¹⁸F-FDG

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

Interventions

89Zr-DFO-Mirvetuximab PET/CTOTHER

Two weeks prior to the start of the trial, laboratory test results including complete blood count, urinalysis, blood biochemistry, and electrocardiogram, as well as imaging findings, will be collected. Within one week after trial initiation, one ¹⁸F-FDG PET scan (at 1 h post-injection) and three ⁸⁹Zr-DFO-Mirvetuximab PET scans (at 24 h, 72 h, and 144 h post-injection) will be performed. Two months after trial completion, pathological examination results will be obtained and compared with the PET imaging findings

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients with newly diagnosed stage IV ovarian cancer or first-recurrent ovarian cancer, aged \>18 years. 2. No clinically significant abnormalities in complete blood count, liver function, or renal function. 3. Estimated life expectancy ≥6 months. 4. At least one measurable target lesion per RECIST version 1.1. 5. Women of childbearing age (15-49 years) must have a negative pregnancy test within 7 days prior to the start of the study procedures; patients with reproductive potential must agree to use effective contraception to avoid pregnancy during the study and within 3 months after the last imaging examination. 6. Female patients must adopt effective contraceptive measures throughout the study period and for 6 months after study completion. 7. Patients must fully understand and voluntarily participate in the trial, and provide written informed consent. Exclusion Criteria: 1. Severe hepatic or renal dysfunction. 2. Women who are planning pregnancy, pregnant, or breastfeeding. 3. Inability to remain supine for 30 minutes. 4. Inability to provide informed consent. 5. Claustrophobia or other psychiatric disorders. 6. Known allergy to the investigational drug or its excipients. 7. Any other condition that the investigator deems unsuitable for participation in the trial.

89Zr-DFO-Mirvetuximab PET/CT Imaging for Companion Diagnosis and Response Evaluation in Ovarian Cancer

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Central Contacts