XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer

This trial will include 2 portions (phase 1 and phase 2). The first portion will be a Phase I, open label, dose escalation study to establish the maximum tolerated dose (MTD) of XB2001 as measured by Dose-Limiting Toxicity (DLT), in combination with ONIVYDE + LV + 5-FU chemotherapy regimen in patients with advanced pancreatic cancer and to determine the recommended dose for the subsequent Phase 2 study. The phase 2 portion will be implemented with the maximum established tolerated dose (MTD) of XB2001. The target enrollment in the phase 2 portion is 60 patients which will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).

Inclusion Criteria: * Histologically or cytologically confirmed pancreatic adenocarcinoma of exocrine pancreas that is metastatic, unresectable, or recurrent * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumor V1.1 * Documented disease progression after one prior gemcitabine-based therapy OR one FOLFIRINOX and gemcitabine combination therapy * Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 or Karnofsky performance status (KPS) ≥ 70 * Adequate hepatic, renal and bone marrow function Exclusion Criteria: * Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration * Clinically significant GI disorders * Severe arterial thromboembolic events less than 6 months before inclusion * Prior Whole Brain Radiation Therapy (WBRT) * Evidence of brain metastases * NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg) * Use of strong CYP3A4 inducers or inhibitors and/or UGT1A1 inhibitors within 14 days prior to Visit 1/Baseline visit.