MIRASOL: A Randomized, Open-label, Phase 3 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

1. Female patients >= 18 years of age
2. Patients must have a confirmed diagnosis of high-grade serous EOC, primary
peritoneal cancer, or fallopian tube cancer
3. Patients must have platinum-resistant disease
a. 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 last dose of
platinum
b. 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.; Patients who are platinum-refractory during front-line treatment
are excluded (see exclusion criteria)
4. Patients must have progressed radiographically on or after their most recent
line of therapy
Note: Progression must be determined radiographically and/or by CA-125 GCIG
progression criteria
5. 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 immunohistochemistry (IHC) confirmation of FRα
positivity
6. Patient's tumor must be positive for FRα expression as defined by the
Ventana FOLR1 (FOLR-2.1) CDx assay
7. Patients must have at least one lesion that meets the definition of
measurable disease by RECIST v1.1 (radiologically measured by the
Investigator)
8. 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:
a. Adjuvant ± neoadjuvant considered one line of therapy
b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as
part of the preceding line of therapy (ie, not counted
independently)
c. Therapy changed due to toxicity in the absence of progression will be
considered as part of the same line (ie, not counted independently)
d. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance.
9. Patient must have an Eastern Cooperative Oncology Group Performance Status
(ECOG PS) of 0 or 1
10. Time from prior therapy:
a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is
shorter)
b. Focal radiation completed at least 2 weeks prior to first dose of study drug
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all
prior therapy-related toxicities
12. 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
13. Patients must have adequate hematologic, liver and kidney functions defined
as:
a. Absolute neutrophil count (ANC) >= 1.5 x 109/L (1,500/µL) without G-CSF in
the prior 10 days or long-acting WBC growth factors in the prior 20 days
b. Platelet count >= 100 x 109/L (100,000/µL) without platelet transfusion in
the prior 10 days
c. Hemoglobin >= 9.0 g/dL without packed red blood cell (PRBC) transfusion in
the prior 21 days
d. Serum creatinine <= 1.5 x upper limit of normal (ULN)
e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3.0 x
ULN
f. Serum bilirubin <= 1.5 x ULN (patients with documented diagnosis of Gilbert
syndrome are eligible if total bilirubin < 3.0 x ULN)
g. Serum albumin >= 2 g/dL
14. 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
15. Women of childbearing potential (WCBP) must agree to use highly effective
contraceptive method(s) in while on study drug and for at least 3 months after
the last dose of mirvetuximab soravtansine or at least 6 months after the last
dose of Pac, PLD, or Topo
16. WCBP must have a negative pregnancy test within 4 days prior to the first
dose of study drug

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous
histology, mixed tumors containing any of the above histologies, or lowgrade
or borderline ovarian tumor
2. 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
3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of
the bone marrow
4. Patients with > Grade 1 peripheral neuropathy per Common
Terminology Criteria for Adverse Events (CTCAE)
5. 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
6. Patients with serious concurrent illness or clinically relevant active
infection, including, but not limited to the following:
a. Active hepatitis B or C infection (whether or not on active antiviral
therapy)
b. HIV infection
c. Active cytomegalovirus infection
d. 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
7. Patients with history of multiple sclerosis or other demyelinating disease
and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
8. Patients with clinically significant cardiac disease including, but not
limited to, any one of the following:
a. Myocardial infarction <= 6 months prior to first dose
b. Unstable angina pectoris
c. Uncontrolled congestive heart failure (New York Heart Association >
class II)
d. Uncontrolled >= Grade 3 hypertension (per CTCAE)
e. Uncontrolled cardiac arrhythmias
9. 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
10. Patients with a history of hemorrhagic or ischemic stroke within six
months prior to randomization
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B
or C)
12. Patients with a previous clinical diagnosis of non-infectious
interstitial lung disease (ILD), including noninfectious pneumonitis
13. Patients with required use of folate-containing supplements (eg, folate
deficiency)
14. Patients with prior hypersensitivity to monoclonal antibodies
15. Women who are pregnant or lactating
16. Patients with prior treatment with MIRV or other FRα-targeting agents
17. Patients with untreated or symptomatic central nervous system
(CNS) metastases
18. 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)
19. Prior known hypersensitivity reactions to study drugs and/or any of their
excipients
20. 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
21. Simultaneous participation in another research study, in countries or
localities where this is the health authority guidance