Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

This is a Phase I/II trial designed to evaluate the combination of the immunotherapeutic
agent indoximod and the standard of care chemotherapy gemcitabine plus nab-paclitaxel in
subjects with metastatic adenocarcinoma of the pancreas. The phase 1 portion is designed to
identify the regimen-limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the
combination. The phase 2 portion of the study will evaluate the potential efficacy of this
combination. All subjects will receive the standard 28-day gemcitabine plus nab-paclitaxel
regimen. Twice daily oral indoximod will be administered concurrently in continuous 28 day
cycles.

In the phase 1 portion, dose escalation of indoximod will begin at 600 mg twice a day and
potentially escalate to 1200 mg twice a day. There will be no intra-subject dose escalation.
Regimen-limiting toxicity will be considered as those toxicities related to indoximod that
significantly limit the administration of the backbone chemotherapy gemcitabine plus
nab-paclitaxel. The period for determination of dose-limiting toxicities will be the initial
28 days of treatment. The recommended phase 2 dose will include an assessment of toxicities
that occur at later time points.

Once a RP2D is determined, the phase 2 portion of the study will be initiated. In both phase
1 and phase 2, every 2 cycles subjects will have repeat imaging to assess response. Corollary
biomarkers will be assessed at the same interval as will PET-CT after the 1st 8 week cycle.
Up to 18 patients will be enrolled in the phase 1 portion of the study and 80 patients will
be enrolled in the phase 2 portion.

Inclusion Criteria:

- Patient has definitive histologically or cytologically confirmed metastatic
adenocarcinoma of the pancreas. Patients with islet cell or neuroendocrine neoplasms
are excluded.

- Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in
the study.

- Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4
weeks prior to entry into the study

- Male or non-pregnant and non-lactating female, and ≥18 years of age.

- Patients must have received no previous radiotherapy, surgery, chemotherapy or
investigational therapy for the treatment of metastatic disease.

- Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is
allowed, provided at least 6 months have elapsed since completion of the last dose and
no lingering toxicities are present.

- Patients cannot have received any other immunomodulatory therapies (including
vaccines) as treatment for this or any other cancer.

- Patient has a Karnofsky performance status (KPS) ≥ 70.

- Patients should be asymptomatic for jaundice prior to Day 1.

Exclusion Criteria:

- Patients may not be receiving (or received prior to enrollment) any other
investigational agents for metastatic disease.

- Patient has known brain metastases,

- Patient has only locally advanced disease.

- Lymph node only metastases even if considered M1 disease by official staging criteria.

- History of malignancy in the last 3 years. Patients with prior history of in situ
cancer or basal or squamous cell skin cancer are eligible. Patients with other
malignancies are eligible if they were cured by surgery alone or surgery plus
radiotherapy and have been continuously disease-free for at least 3 years.

- Patients with any active autoimmune disease

- Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done
to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to
Day 1 of treatment in this study.