An Efficacy and Safety Study of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Adults With Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly Patients With Acute Myeloid Leukemia (AML)

Inclusion Criteria

For both cohorts:

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Female subjects of childbearing potential may participate, providing they meet the following conditions:
• Have 2 negative pregnancy tests as verified by the Investigator prior to starting any investigational product (IP) therapy: serum pregnancy test at screening and negative serum or urine pregnancy test (Investigator's discretion) within 72 hours prior to starting treatment with IP (Cycle 1, Day 1). They must agree to ongoing pregnancy testing during the course of the study (before beginning each subsequent cycle of treatment), and after the last dose of any IP. This applies even if the subject practices complete abstinence from heterosexual contact.
• Agree to practice true abstinence (which must be reviewed on a monthly basis and source documented) or agree to the use of a highly effective method of contraception use from 28 days prior to starting durvalumab or azacitidine, and must agree to continue using such precautions while taking durvalumab or azacitidine (including dose interruptions) and up to 90 days after the last dose of durvalumab or azacitidine. Cessation of contraception after this point should be discussed with a responsible physician.
• Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of IP.
• Refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.
• Male subject must:
• Either practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to avoid fathering a child, to use highly effective methods of contraception, male condom plus spermicide during sexual contact with a pregnant female or a female of childbearing potential (even if he has undergone a successful vasectomy) from starting dose of IP (Cycle 1 Day 1), including dose interruptions through 90 days after receipt of the last dose of durvalumab or azacitidine.
• Refrain from semen or sperm donation while taking IP and for at least 90 days after the last dose of IP.
• Understand and voluntarily sign a biomarker-specific component of the informed consent form prior to any study-related procedures conducted.
• Willing and able to adhere to the study visit schedule and other protocol requirements.

MDS Cohort:

• Age ≥ 18 years at the time of signing the informed consent form.
• Central confirmation of diagnosis of previously untreated primary or secondary myelodysplastic syndromes (MDS) as per World Health Organization (WHO) classification. Results of central pathology review are required prior to receiving the first dose of IP.
• Central confirmation of the categorization of the MDS risk classification, as per the Revised - International prognostic scoring system (IPSS-R) Intermediate risk with >10% blasts or poor or very poor cytogenetics, or IPSS-R High or Very High risk (results of central pathology review required prior to receiving the first dose of IP).

Acute myeloid leukemia (AML) Cohort:

• Age ≥ 65 years at the time of signing the informed consent form (ICF).
• Central confirmation of diagnosis of one of the following untreated AML as per WHO classification:
• Newly diagnosed, histologically confirmed de novo AML (bone marrow blasts ≥ 20%), or
• AML secondary to prior MDS, or
• AML secondary to exposure to potentially leukemogenic therapies or agents (eg, radiation therapy, alkylating agents, topoisomerase II inhibitors) with the primary malignancy in remission for at least 2 years.
• Central confirmation of intermediate or poor risk status, based on Cytogenetics for acute myeloid leukemia.

Exclusion Criteria

For both cohorts:

• Prior hematopoietic stem cell transplant.
• Considered eligi