Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas that has not
been previously treated in the metastatic setting

- Unresectable, locally advanced or metastatic disease; diagnosed within 6 weeks prior
to screening

- At least one tumor lesion measurable by CT or MRI scan (according to RECIST v1.1)

- ECOG performance status of 0 or 1 at screening and within 72 hours prior to first dose
if first dose occurs more than 72 hours post-screening

- Adequate hematological, hepatic, renal and cardiac function

- Recovered from the effects of any prior surgery or radiotherapy

- Patient has a Karnofsky performance status (KPS) ≥ 70 at Screening, and within 72
hours prior to date of first dose if first dose occurs more than 72 hours after
screening (Part 1B only)

Exclusion Criteria:

- Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced
setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or
investigational therapy

- Prior treatment of pancreatic cancer with chemotherapy in adjuvant setting, except
those where at least 12 months have elapsed since completion of the last dose and no
persistent treatment-related toxicities present

- Uncontrolled Central Nervous System (CNS) metastases

- Clinically significant gastrointestinal disorder

- History of any second malignancy in the last 3 years. Patients with prior history of
in-situ cancer or basal or squamous cell skin cancer are eligible

- Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin,
oxaliplatin

- Use of strong CYP3A4 or inducers or presence of any other contra indications for
irinotecan

- Pregnant or breast feeding

- Neuroendocrine or acinar pancreatic carcinoma

- Serum albumin < 3 g/dL at screening visit and within 72 hours prior to first dose if
first dose occurs more than 72 hours post screening

- Patients with symptoms and signs of clinically unacceptable deterioration of primary
disease at time of screening

- Previous treatment with irinotecan-based, nab-paclitaxel-based or gemcitabine-based
resulting in disease progression