Mirvetuximab Soravtansine for the Treatment of Folate Receptor-Alpha Positive Persistent or Recurrent Endometrial Cancer

Inclusion Criteria

• Patients must have radiologically confirmed (ie, computed tomography [CAT] scan and/or magnetic resonance imaging [MRI]) persistent or recurrent EC
• All patients must have one of the following pathologically documented, definitively diagnosed tumor types: * Uterine serous carcinoma (pure or mixed) * Grade 3 endometrial adenocarcinoma * Carcinosarcoma with high grade serous or G2/G3 endometrioid components * Clear cell carcinoma (pure or mixed)
• All patients must have measurable disease. Measurable disease is defined as lesions which can be measured by physical examination or by means of medical imaging techniques. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be >= 20 mm when measured by conventional techniques, including palpation or plain x-ray, or >= 10 mm when measured by spiral computed tomography (CT) and/or MRI. Ascites and pleural effusions are not to be considered measurable disease
• Patients must be willing to provide an archival tumor tissue block or slides and must have confirmation of FRalpha positivity by the Ventana FOLR2.1 immunohistochemistry (IHC) or equivalent Food and Drug Administration (FDA)-approved assay * Must have FRalpha-positivity >= 50% 2+ of tumor FRalpha staining
• Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by RECIST version (v) 1.1. Tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence following completion of radiation therapy
• Prior treatment with =< 3 prior lines of therapy for recurrent disease; hormonal agents are not considered a line of therapy; prior treatment with folate receptor-targeting investigational agents is not allowed
• After undergoing surgery, patients may be optimally or sub optimally debulked
• >= 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Time from prior therapy: * Systemic anti-neoplastic therapy: five half-lives or three weeks, whichever is shorter * Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least four weeks, or focal radiation completed at least two weeks, prior to starting study treatment
• Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy to grade 1 or less (except alopecia)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1,500/uL)
• Platelet count >= 100 x 10^9/L (100,000/uL); must not be transfused within previous 10 days
• Hemoglobin >= 9.0 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or 24-hour creatinine clearance of >= 60 mL/minute
• Aspartate aminotransferase (AST) =< 2.5 x ULN; alanine aminotransferase (ALT) =< 2.5 x ULN
• Serum bilirubin =< 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
• Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements
• Women of child bearing potential (WCBP), must agree to use effective contraceptive methods during study treatment and for at least twelve weeks after the last dose of IMGN853
• WCBP must have a negative pregnancy test within 4 days prior to the first dose of study treatment
• As men do not have uteri, only women will be enrolled in this trial. Participating institutions will not exclude potential subjects from participating in this or any study solely based on ethnic origin or socioeconomic status. Every attempt will be made to enter all eligible patients into this protocol and therefore address the study objectives in a patient population representative of the entire recurrent endometrial cancer population treated by participating institutions

Exclusion Criteria

• Active or chronic corneal disorder (grade 1 or higher at baseline), including but not limited to the following: Sjogren’s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
• Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following: * Known active hepatitis B or C * Known human immunodeficiency virus (HIV) infection * Varicella-zoster virus (shingles) * Cytomegalovirus infection * Any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment
• Clinically-significant cardiac disease such as recent myocardial infarction (=< 6 months prior to day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart Association > class II), uncontrolled hypertension (>= Common Terminology Criteria for Adverse Events [CTCAE] v 5.0 grade 3), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled cardiac arrhythmias, clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting aneurysm), severe aortic stenosis, clinically significant peripheral vascular disease, or >= grade 3 cardiac toxicity following prior chemotherapy
• History of neurological conditions that would confound assessment of treatment-emergent neuropathy
• History of hemorrhagic or ischemic stroke within the last 6 months
• History of cirrhotic liver disease
• Previous clinical diagnosis of non-infectious pneumonitis
• Prior hypersensitivity to monoclonal antibodies
• Women who are pregnant or lactating or expecting within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
• Carcinomatous meningitis, untreated central nervous system (CNS) disease or symptomatic CNS metastasis. Patients with previously treated CNS metastasis (excluding carcinomatous meningitis) may participate if they are stable (without evidence of progression by imaging, using identical imaging modality at each assessment, for at least 4 weeks prior to first dose of study treatment), have no evidence of new or emerging CNS metastasis, and are not using steroids for at least 7 days prior to first dose of study treatment
• History or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment
• Required used of folate-containing supplements (e.g. folate deficiency)
• Has a known additional malignancy that is progressing or required active treatment within 3 years of first dose of study treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or other in situ cancers