MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) With or Without Durvalumab in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma

The objective of this study is to evaluate the safety, tolerability, and antitumor activity of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in participants with metastatic pancreatic cancer.

This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to assess the safety, preliminary antitumor activity, immunogenicity, and pharmacokinetics (PK) of oleclumab with or without durvalumab in combination with chemotherapy administered in participants with metastatic pancreatic ductal adenocarcinoma (PDAC). Participants with previously untreated metastatic PDAC (first-line [1L] metastatic PDAC) will be enrolled in Cohort A. Participants with metastatic PDAC previously treated with gemcitabine-based chemotherapy (without exposure to 5-fluorouracil [5-FU], capecitabine, or oxaliplatin; second-line [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. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

4. Weight >= 35 kg

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

   Cohort A: Participants with previously untreated metastatic pancreatic adenocarcinoma (1L metastatic disease) not previously treated with systemic therapies Cohort B: Participants with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2L metastatic disease

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

7. All Participants 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. Participants with a history of venous thrombosis within the past 3 months
5. Participants 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.