Overview
Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRα). It is being developed as maintenance therapy for the treatment of subjects with recurrent platinum-sensitive, highgrade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Patients must have confirmation of FRα positivity by the Ventana FOLR1 Assay.
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Principal investigator
Eligibility criteria
Exclusion Criteria: 1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade/borderline ovarian tumor 2. More than one line of prior chemotherapy before current/planned triplet therapy. Lines of prior anticancer therapy are counted with the following considerations: 1. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens. 2. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently). 3. Change due to toxicity will be considered part of the proceeding line of therapy. 3. Patients with PD while on or following platinum-based triplet therapy 4. After completion of triplet therapy and prior to randomization: Patients who receive an intervening dose of bevacizumab after the last dose of triplet therapy before randomization 5. Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow 6. Patients with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) 7. 7. Patients with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision 8. Patients with serious concurrent illness or clinically relevant active infection, including but not limited to the following: 1. Active hepatitis B or C infection (whether or not on active antiviral therapy) 2. HIV infection 3. Active cytomegalovirus infection 4. Any other concurrent infectious disease requiring intravenous (IV) antibiotics within 2 weeks before the first dose of maintenance therapy Note: Testing at screening is not required for the above infections unless clinically indicated. 9. Patients with a history of multiple sclerosis or other demyelinating diseases and/or Lambert-Eaton syndrome (paraneoplastic syndrome) 10. Patients with clinically significant cardiac disease including, but not limited to, any of the following: 1. Myocardial infarction ≤ 6 months prior to C1D1 of maintenance treatment 2. Unstable angina pectoris 3. Uncontrolled congestive heart failure (New York Heart Association \> class II) 4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) 5. Uncontrolled cardiac arrhythmias 11. Patients with a history of hemorrhagic or ischemic stroke within 6 months before enrollment 12. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C) 13. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings) 14. History of bowel obstruction (including sub-occlusive disease) related to underlying disease within 6 months before the start of maintenance study treatment (triplet therapy for Run-In patients). 15. History of abdominal fistula or gastrointestinal perforation 16. Intra-abdominal abscess, evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction within 4 weeks prior to randomization (or within 4 weeks prior to starting triplet therapy for Run- In patients) 17. Clinically significant proteinuria: urine-protein to creatinine (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24-hour urine collection and must show result ≤ 1 g of protein in a 24-hour period. 18. History of Grade 4 thromboembolic events 19. Patients not appropriate for bevacizumab 15 mg/kg dosing at the start of maintenance therapy as per the treating physician 20. Patients requiring use of folate-containing supplements (eg, folate deficiency) 21. Patients with prior hypersensitivity to monoclonal antibodies (mAbs) 22. Women who are pregnant or breastfeeding 23. Patients who received prior treatment with MIRV or other FRα-targeting agents 24. Patients with untreated or symptomatic central nervous system metastases 25. Patients with a history of other malignancy within 3 years prior to signing study consent Note: Patients with tumors with a negligible risk for metastasis or death (eg, controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible. 26. Prior known hypersensitivity reactions to study drugs or any of their excipients
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