Gender
Female
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Female participants ≥ 18 years of age
2. Participants must have a confirmed diagnosis of high-grade serious epithelial
ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
3. Participants must have platinum-resistant disease:
1. Participants 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
2. Participants 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: Participants who are platinum-refractory during front-line
treatment are excluded
4. Participants must have progressed radiographically on or after their most recent
line of therapy
5. Participants 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. Participant's tumor must be positive for FRα expression as defined by the Ventana
FOLR1 (FOLR-2.1) CDx assay
7. Participants must have at least one lesion that meets the definition of measurable
disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
(radiologically measured by the Investigator)
8. Participants 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:
1. Adjuvant ± neoadjuvant considered one line of therapy
2. Maintenance therapy (for example, bevacizumab, poly (ADP-ribose) polymerase
[PARP] inhibitors) will be considered as part of the preceding line of therapy
(that is, not counted independently)
3. Therapy changed due to toxicity in the absence of progression will be
considered as part of the same line (that is, not counted independently)
4. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance
9. Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG
PS) of 0 or 1
10. Time from prior therapy:
1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
2. Focal radiation completed at least 2 weeks prior to first dose of study drug
11. Participants 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. Participants must have adequate hematologic, liver and kidney functions defined as:
1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/liter (L) (1,500/microliter [μL])
without granulocyte colony-stimulating factor (G-CSF) in the prior 10 days or
long-acting white blood cell (WBC) growth factors in the prior 20 days
2. Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the
prior 10 days
3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the
prior 21 days
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
6. Serum bilirubin ≤ 1.5 x ULN (participants with documented diagnosis of Gilbert
syndrome are eligible if total bilirubin < 3.0 x ULN
7. Serum albumin ≥ 2 grams (g)/deciliter (dL)
14. Participants 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) 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
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of
study drug
Exclusion Criteria:
1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology,
mixed tumors containing any of the above histologies, or low-grade or borderline
ovarian tumor
2. Participants 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. Participants with prior wide-field radiotherapy (RT) affecting at least 20% of the
bone marrow
4. Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteria
for Adverse Events (CTCAE) v5.0
5. Participants 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. Participants with serious concurrent illness or clinically relevant active
infection, including, but not limited to the following:
1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
2. Human immunodeficiency virus (HIV) infection
3. Active cytomegalovirus infection
4. 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. Participants with history of multiple sclerosis or other demyelinating disease
and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
8. Participants with clinically significant cardiac disease including, but not limited
to, any one of the following:
1. Myocardial infarction ≤ 6 months prior to first dose
2. Unstable angina pectoris
3. Uncontrolled congestive heart failure (New York Heart Association > class II)
4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
5. Uncontrolled cardiac arrhythmias
9. Participants 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. Participants with a history of hemorrhagic or ischemic stroke within six months
prior to randomization
11. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Participants with a previous clinical diagnosis of non-infectious interstitial lung
disease (ILD), including noninfectious pneumonitis
13. Participants with required use of folate-containing supplements (for example, folate
deficiency)
14. Participants with prior hypersensitivity to monoclonal antibodies
15. Women who are pregnant or lactating
16. Participants with prior treatment with MIRV or other FRα-targeting agents
17. Participants with untreated or symptomatic central nervous system (CNS) metastases
18. Participants 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 (for example, 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