Inclusion Criteria

• Must sign an approved informed consent form
• Age ≥ 18 years
• Must have pathology-confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
• Must have primary or secondary platinum-resistant ovarian cancer
• Must have at least a single (RECIST v1.1-defined) measurable lesion
• For the purpose of obtaining a RECIST v1.1 baseline scan,  must have a radiological evaluation conducted no more than 28 days prior to beginning study therapy (PLD)
  • For a history of CNS metastasis, baseline radiological imaging must include an evaluation of the head
• Must have had prior debulking surgery
• Must have received prior platinum-based chemotherapy for management of primary disease but must not have received more than 2 prior systemic cytotoxic regimens
• Allowed to have received, but not required to have received, one additional non-cytotoxic antitumor agent (eg, biologic or cytostatic) for the management of ovarian cancer
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Must have recovered (to baseline/stabilization) from prior cytotoxic therapy-associated acute toxicities
• Must have adequate organ function including
  • Bone Marrow Reserve
    • Use of supportive care measures (eg, use of white blood cell [WBC] growth factors, antiemetics, epoetin) should follow the ASCO guidelines as listed at www.asco.org
    • Participants should receive full supportive care, including transfusion of blood as mandated by clinical need
    • Transfusions administered for the sole purpose of meeting the study inclusion criteria between the time informed consent is signed and first dose of EC145/placebo/PLD is administered are not allowed
    • Hemoglobin ≥ 9 g/dL
    • Platelets ≥ 100x10^9/L
    • Absolute neutrophil count (ANC) ≥ 1.5x10^9/L prior to treatment
    • Maintenance doses of granulocyte colony stimulating factor (G-CSF) are eligible
  • Hepatic
    • Total bilirubin level < 1.5 x ULN 
    • ALT, AST, GGT, and alkaline phosphatase levels < 2.5 x ULN
  • Renal
    • Serum creatinine level ≤ 1.5 x ULN 
    • For creatinine levels above 1.5 x ULN, creatinine clearance ≥ 50 mL/min/1.73m^2
  • Cardiac
    • Left ventricular ejection fraction (LVEF) equal to or greater than the institutional lower limit of normal

Exclusion Criteria

• Refractory to primary platinum therapy where "refactory" is defined as disease progression within 6 months of first dose of initial platinum-based therapy
• Diagnosis of "tumor of low-malignant potential"
• Prior exposure to PLD or anthracycline therapy
• Prior exposure to FR-targeted therapy (eg, EC145, EC0225, EC0489, farletuzumab)
• Prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds
• Prior abdominal or pelvic radiation therapy or radiation therapy to > 10% of the bone marrow at any time in the past or prior radiation therapy within the past 3 years to the breast/sternum, dermal lesions, head or neck
• Recent (i.e., ≤ 6 weeks) history of abdominal surgery or peritonitis
• Serious comorbidities (as determined by the investigator) such as, but not limited to, active congestive heart failure or recent myocardial infarction
• Require antifolate therapy for the management of comorbid conditions (e.g., rheumatoid arthritis)
• Pregnant or nursing
• Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ)
• Symptomatic central nervous system (CNS) metastasis
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation)
  • Use of low dose corticosteroid therapy (e.g., for nausea prophylaxis) is acceptable
• Concomitant tamoxifen therapy
  • Supportive care measures are allowed