Inclusion Criteria:

• Female patients ≥ 18 years of age.
• Patients must have a confirmed diagnosis of high-grade serous EOC, 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 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 (see exclusion criteria).
• 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 immunohistochemistry (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 (e.g., bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (i.e., not counted independently);
  • Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (i.e., 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 f. 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) in 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 Pac, PLD, or Topo.
• 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 Common Terminology Criteria for Adverse Events (CTCAE).
• 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 LambertEaton 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 (e.g., 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 (e.g., 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.