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

Laborértékek

• Non-serous histological subtypes, including endometrioid, clear cell, mucinous, sarcomatous components, mixed histology containing any of these components, or low-grade/borderline ovarian tumors.
  • Primary platinum-refractory disease (failure to achieve CR/PR to first-line platinum therapy or progression within 3 months after last platinum dose).
  • Prior wide-field radiation therapy involving ≥20% of bone marrow.
  • Baseline peripheral neuropathy > Grade 1 according to CTCAE v5.0.
  • 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).
  • History of multiple sclerosis, other demyelinating diseases, or Lambert-Eaton myasthenic syndrome.
  • 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 hepatic cirrhosis (Child-Pugh Class B or C).
  • History of bowel obstruction (including subileus) related to underlying disease within 6 months prior to study initiation.
  • Presence of any of the following:
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess;
  • Pelvic examination or CT scan indicating rectosigmoid/gastrointestinal involvement, or clinical signs/symptoms of intestinal obstruction.
  • Non-healing wounds, active ulcers, or bone fractures.
  • Hemoptysis (≥0.5 teaspoon / ~2.5 mL of fresh red blood per episode) within 4 weeks prior to first dose.
  • History of Posterior Reversible Encephalopathy Syndrome (PRES).
  • 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.
  • History of pulmonary embolism.
  • History of Grade 4 thromboembolic events.
  • Prior treatment with mirvetuximab soravtansine, other FRα-targeting agents, or suvemcitug.
  • Untreated or symptomatic central nervous system (CNS) metastases.
  • 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).
  • Pregnant or breastfeeding females.
  • 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.

• 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.