A Multi-Cancer, Multi-State, Platform Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck to Correlate Clinical, Molecular and Immunologic Parameters With DNA Methylation

Inclusion Criteria:

1. Age ≥ 18 years at the time of screening or age of consent
2. Written informed consent and any locally required authorization (eg, data privacy) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
3. ECOG of 0 or 1
4. Weight ≥ 35 kg
5. Must have a life expectancy of at least 12 weeeks
6. Histological or cytological confirmation
7. At least 1 measurable lesion according to RECIST version 1.1
8. Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative biomarker studies are required (1 H\&E and 15 unstained slides) unless no such sample is available or insufficient sample exists. Subjects with insufficient archived tumor samples are still eligible
9. Adequate organ and marrow function
10. Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening to 180 days after the final dose of study treatment
11. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 180 days after receipt of the final dose of study treatment

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-mediated therapy
3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
4. Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
5. Subjects with a history of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
6. Subjects with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment
7. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
8. HIV, Hep A, B, or C
9. History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
10. Other invasive malignancy within 2 years
11. Known allergy or hypersensitivity to investigational product formulations
12. History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
13. Active grade 3 or greater edema
14. Uncontrolled intercurrent illness
15. Any history of leptomeningeal disease or cord compression
16. Untreated CNS metastatic disease.
17. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment.
18. Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
19. Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
20. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
21. Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
22. Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results