MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study

This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to
assess the safety, preliminary antitumor activity, immunogenicity, and PK of oleclumab with
or without durvalumab in combination with chemotherapy administered in subjects with
metastatic PDAC. Subjects with previously untreated metastatic PDAC (1L metastatic PDAC) with
be enrolled in Cohort A. Subjects with metastatic PDAC previously treated with
gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, or oxaliplatin, 2L
metastatic PDAC) will be enrolled in Cohort B. The study consists of 2 parts, dose escalation
(part 1) and dose expansion (Part 2).

Inclusion Criteria:

1. Age ≥ 18

2. Written and signed informed consent must be obtained

3. ECOG Performance Status 0 or 1

4. Weight ≥ 35 kg

5. Subjects must have histologically or cytologically, confirmed pancreatic
adenocarcinoma:

Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1st
line metastatic disease) not previously treated with systemic therapies.

Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with
gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin)
2nd line metastatic disease

6. Subjects must have at least 1 measurable lesion according to RECIST v1.1

7. All subjects must consent to providing archival tumor specimens

Exclusion Criteria:

1. Receipt of any conventional or investigational anticancer therapy within 21 days or
palliative radiotherapy within 14 days prior to the scheduled first dose of study
treatment.

2. Prior receipt of any immune-related therapy

3. Concurrent enrollment in another therapeutic clinical study. Enrollment in
observational studies will be allowed

4. Subjects with a history of venous thrombosis within the past 3 months

5. Subjects with prior history of myocardial infarction, transient ischemic attack, or
stroke in the last 3 months prior to start of treatment

6. Active or prior documented autoimmune or inflammatory disorders within the past 3
years prior to the start of treatment

7. Other invasive malignancy within 2 years.

8. Any history of leptomeningeal disease or cord compression.

9. Current or prior use of immunosuppressive medication within 14 days prior to the first
dose