Mirvetuximab Soravtansine Combined With Suvemcitug in Platinum-Resistant Recurrent Ovarian Cancer

Prior treatment

• Prior wide-field radiation therapy involving ≥20% of bone marrow.
• Uncontrolled severe systemic comorbid conditions (e.g., active infection, non-infectious interstitial lung disease, or clinically significant cardiovascular/cerebrovascular events within 6 months prior to first dose) rendering the patient unsuitable for the study.
• History of hemorrhagic or ischemic stroke within 6 months prior to randomization/enrollment.
• History of bowel obstruction (including subileus) related to underlying disease within 6 months prior to study initiation.
• Hemoptysis (≥0.5 teaspoon / \~2.5 mL of fresh red blood per episode) within 4 weeks prior to first dose.
• Prior treatment with mirvetuximab soravtansine, other FRα-targeting agents, or suvemcitug.
• Malignancy within 3 years prior to enrollment, except for localized cancers treated with curative intent with negligible risk of metastasis or death (e.g., adequately treated basal cell/squamous cell skin cancer or carcinoma in situ of the cervix/breast).

Other illness

• Primary platinum-refractory disease (failure to achieve CR/PR to first-line platinum therapy or progression within 3 months after last platinum dose).
• History of multiple sclerosis, other demyelinating diseases, or Lambert-Eaton myasthenic syndrome.
• History of hepatic cirrhosis (Child-Pugh Class B or C).
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess;
• History of Posterior Reversible Encephalopathy Syndrome (PRES).
• History of pulmonary embolism.
• History of Grade 4 thromboembolic events.
• Known hypersensitivity to any of the study intervention drugs or excipients.
• Any other condition that, in the opinion of the investigator, makes the patient unsuitable for trial participation.

Lab values

• Clinically significant proteinuria: Urine Protein/Creatinine Ratio (UPC) ≥ 1.0 or dipstick protein ≥ 2+; if UPC ≥ 1.0 or dipstick ≥ 2+, 24-hour urine protein quantification must be ≤ 1.0 g/24h to be eligible.

Age

• Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing medication/monitoring (e.g., uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic macular edema, macular degeneration, papilledema, and/or monocular vision).

Other

• \- Non-serous histological subtypes, including endometrioid, clear cell, mucinous, sarcomatous components, mixed histology containing any of these components, or low-grade/borderline ovarian tumors.
• Baseline peripheral neuropathy \> Grade 1 according to CTCAE v5.0.
• Presence of any of the following:
• Pelvic examination or CT scan indicating rectosigmoid/gastrointestinal involvement, or clinical signs/symptoms of intestinal obstruction.
• Non-healing wounds, active ulcers, or bone fractures.
• Untreated or symptomatic central nervous system (CNS) metastases.
• Pregnant or breastfeeding females.

• \- Voluntary written informed consent signed prior to any study-related procedures.
• Female age ≥ 18 years at the time of signing informed consent.
• Histologically confirmed high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
• Documented platinum-resistant recurrence, defined as progression within 6 months after completion of the last platinum-based chemotherapy regimen (excluding primary platinum-refractory disease, defined as progression during or within 3 months of first-line platinum-based therapy).
• Radiologically confirmed disease progression during or following the most recent line of therapy.
• FRα-positive tumor status verified by the Ventana FOLR1 (FOLR-2.1) CDx IHC assay, defined as ≥25% of tumor cells showing ≥2+ membrane staining intensity.
• Presence of at least one measurable lesion according to RECIST v1.1 guidelines as evaluated by investigator imaging.
• Must have received 1 to 3 prior systemic antineoplastic therapy lines.
• Must have received prior treatment with bevacizumab.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate washout period from prior antineoplastic therapy: ≥5 half-lives or ≥4 weeks for systemic therapy (whichever is shorter); ≥2 weeks for localized palliative radiotherapy.
• Recovery or stabilization of all toxicities from prior therapies to Grade ≤1 or baseline (NCI CTCAE v5.0).
• Major surgery completed at least 4 weeks prior to initiation of study treatment, with postoperative toxicities recovered or stabilized.
• Adequate bone marrow, hepatic, and renal organ functions.