Study of HPN536 in Patients With Advanced Cancers Associated With Mesothelin Expression

• One of the following progressive advanced or metastatic cancers:

• Epithelial ovarian, fallopian tube, or primary peritoneal cancer that is platinum refractory or platinum resistant
• Pancreatic adenocarcinoma that is locally advanced, and now with progressive disease on or after front-line treatment
• Malignant mesothelioma with epithelioid histology, pleural or peritoneal
• For Part 2 only - Measurable disease according to RECIST v1.1 for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, pancreatic adenocarcinoma, and peritoneal mesothelioma, and mRECIST v1.1 for patients with pleural mesothelioma
• Available archival tissue sample, or fresh biopsy tissue sample must be obtained prior to enrollment. For Part 2 only- a fresh biopsy tissue sample is required.
• Adequate bone marrow function, including:

• Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 x 109/L
• Platelets ≥100,000/mm3 or ≥100 x 109/L
• Hemoglobin (Hgb) ≥9 g/dL
• Adequate renal function, including estimated creatinine clearance ≥30 mL/min
• Adequate liver function, including:

• Total serum bilirubin ≤1.5 x upper limit of normal (ULN) unless the patient has documented Gilbert syndrome in which case the maximum total serum bilirubin should be <5 mg/dL
• Aspartate and alanine transaminase (AST and ALT) ≤2.5 x ULN or AST/ALT ≤5 x ULN for patients with liver metastases
• Serum albumin ≥30 mg/mL

Key Exclusion Criteria:

• Brain metastases unless previously treated. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, and have no evidence of new or enlarging brain metastases
• Evidence of retroperitoneal fibrosis, mesothelial surface (pleura, pericardium, peritoneum) thickening of ≥4 mm; significant or increasing pleural/pericardial effusions, ascites or pericarditis at baseline deemed unrelated to the underlying malignancy based on computed tomography (CT), magnetic resonance imaging (MRI), or echocardiogram (ECHO); or prior history of pleurodesis, retroperitoneal fibrosis or mediastinal fibrosis.
• Previous Grade 3/4 infusion or hypersensitivity reaction (not immunotoxicity) to treatment with another monoclonal antibody.
• For patients with tumor types other than pleural mesothelioma: Ascites requiring >1 paracentesis for therapeutic purposes (i.e., not for diagnosis) within 1 month prior to Cycle 1 Day 1.