A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression

Inclusion Criteria:

Female patients ≥ 18 years of age
Patients must have a confirmed diagnosis of high-grade serious epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

Patients must have platinum-resistant disease:

Patients who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between >3 months and ≤ 6 months after the date of the last dose of platinum
Patients who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression. Note: Patients who are platinum-refractory during front-line treatment are excluded
Patients must have progressed radiographically on or after their most recent line of therapy
Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low risk, medically routine procedure for IHC confirmation of FRα positivity
Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)

Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment:

Adjuvant ± neoadjuvant considered one line of therapy
Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently)
Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently)
Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

Time from prior therapy:

Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
Focal radiation completed at least 2 weeks prior to first dose of study drug
Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery

Patients must have adequate hematologic, liver and kidney functions defined as:

Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days
Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN
Serum albumin ≥ 2 g/dL
Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.9.6 in the protocol) while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan
WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug

Exclusion Criteria:

Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy
Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
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

Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

Active hepatitis B or C infection (whether or not on active antiviral therapy)
HIV infection
Active cytomegalovirus infection
Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated
Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

Patients with clinically significant cardiac disease including, but not limited to, any one of the following:

Myocardial infarction ≤ 6 months prior to first dose
Unstable angina pectoris
Uncontrolled congestive heart failure (New York Heart Association > class II)
Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
Uncontrolled cardiac arrhythmias
Patients assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization
Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
Patients with required use of folate-containing supplements (eg, folate deficiency)
Patients with prior hypersensitivity to monoclonal antibodies
Women who are pregnant or lactating
Patients with prior treatment with MIRV or other FRα-targeting agents
Patients with untreated or symptomatic central nervous system (CNS) metastases
Patients with a history of other malignancy within 3 years prior to randomization. Note: does not include tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
Prior known hypersensitivity reactions to study drugs and/or any of their excipients
People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship/curatorship), people who are unable to express their consent, and people who are subject to a legal guardianship order
Simultaneous participation in another research study, in countries or localities where this is the health authority guidance