A Phase 2 Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Multi-Cancer Populations With Correlation to Clinical, Molecular and Immunologic Parameters With DNA MethylaTION

Inclusion Criteria:

1. Age ≥ 18 years at the time of screening or age of consent according to law
2. Life expectancy of at least 12 weeks
3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
4. ECOG 0 or 1
5. Weight ≥35kg
6. Subjects diagnosed with histologically or cytologically confirmed non small cell lung (NSCLC) or renal cell carcinoma (RCC)
7. Subjects must have 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). Subjects with insufficient archived tumor samples are still eligible, pending discussion with the principal investigator on a case by case basis
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 90 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 90 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 agents targeting CD73, including patients treated with adenosine receptor antagonists, CD39 or CD73 inhibitors
3. Prior receipt of any innate immune agonists
4. Patients with NSCLC with known activating EGFR mutations or ALK translocations
5. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
6. Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
7. 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
8. 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
9. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
10. HIV, Hep A, B, or C
11. History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
12. Known allergy or hypersensitivity to investigational product formulations
13. History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
14. Active grade 3 or greater edema
15. History of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
16. Uncontrolled intercurrent
17. Any history of untreated leptomeningeal disease or cord compression
18. Untreated CNS metastatic disease
19. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment
20. Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
21. Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
22. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
23. Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
24. Any condition that would interfere with the evaluation of the study regimen or interpretation of patient safety or study results
25. Any condition that would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results