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)

Time to first response is defined as the time from randomization to the earliest date any response (complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI)) based on International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who did not achieve any defined response were censored at the date of last adequate response assessment, disease progression, or death, whichever occurred first. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Relapse-free survival is defined as the time from the date of first documented response (complete remission (CR), partial remission (PR)) to the date of disease relapse or death from any cause, whichever occurred first according to the International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Participants who received a subsequent therapy before the date of disease relapse or death were censored at the time of subsequent therapy. Relapse after CR or PR is defined as at least one of the following: •Return to pretreatment bone marrow blast % •Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets •Reduction in hemoglobin concentration by ≥ 1.5 g/dL or transfusion dependence. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Cytogenetic response is defined as the percentage of participants who achieved a complete cytogenetic response or partial cytogenetic response according to the International Working Group (IWG) 2006 response criteria and central review. Complete cytogenetic response: Disappearance of the baseline chromosomal abnormality without appearance of new abnormalities. Partial cytogenetic response: At least 50% reduction of the chromosomal abnormality. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD), relapse, or death due to any cause during or after the treatment period, whichever occurred first, according to the International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Progressive disease is defined as follows: - an increase in BM blasts relative to nadir: •If nadir less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts •If nadir 5% - 10% blasts: ≥ 50% increase in blasts to > 10% blasts •If nadir 10% - 20% blasts: ≥ 50% increase in blasts to > 20% blasts •If nadir 20% - 30% blasts: ≥ 50% increase in blasts to > 30% blasts And any of the following: •At least 50% decrement from maximum remission/response levels in granulocytes or platelets •Reduction in Hgb concentration by ≥ 2 g/dL •Transfusion dependence

Duration of response is defined as the time from when the first overall response (complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI)) was observed until relapse, progressive disease (PD), or death, as defined by the International Working Group (IWG) 2006 response criteria and central review. If no relapse, PD, or death was observed, the duration of response was censored at the last response assessment date that the participant was known to be progression-free. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Participants were monitored for transformation to acute myeloid leukemia (AML) until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial. Time to transformation to AML is defined as the time from the date of randomization until the date the participant had documented transformation to AML (defined as at least 30% of myeloblasts in the bone marrow). Participants with no transformation to AML were censored at the date of their last disease assessment.

Disease transformation to acute myeloid leukemia (AML) is defined as at least 30% myeloblasts in the bone marrow. Participants were monitored for transformation to AML until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial. Participants with no transformation to AML were censored at the date of their last disease assessment.

Time to first response is defined as the time between the date of randomization and the earliest date any response (CR or CRi) was observed based on the modified International Working Group (IWG) 2003 response criteria for AML and central review. Participants who did not achieve any defined response were censored at the date of last adequate response assessment, disease progression, or death, whichever occurred first. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Relapse-free survival is defined as time from the date of first documented response (morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi)) to the date of disease relapse or death from any cause, whichever occurred first based on the modified International Working Group (IWG) 2003 response criteria for AML and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Participants who received a subsequent therapy before the date of disease relapse or death were censored at the time of subsequent therapy.

Complete cytogenetic response (CyCR) based on the modified International Working Group (IWG) 2003 response criteria is defined as morphologic complete remission with a reversion to a normal karyotype. The following conditions must be met: • Absolute neutrophil count (ANC) ≥ 1.0 x10⁹/L • Platelet count ≥ 100 x10⁹/L • The bone marrow should contain less than 5% blast cells; • Auer rods should not be detectable; • No platelet, or whole blood transfusions for 7days prior to the date of the hematology assessment. AND • Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases). Response was assessed following every 3 treatment cycles until treatment discontinuation.

Hematological improvement was defined as participants with a erythroid response (HI-E), platelet response (HI-P) or neutrophil response (HI-NE) for at least 8 weeks, according to the IWG 2006 response criteria: Hi-E (in participants with pretreatment hemoglobin < 11 g/dL or red blood cell (RBC)-transfusion dependent): Hemoglobin increase of ≥ 1.5 g/dL, or reduction in units of RBC transfusions of at least 4 RBC transfusions/8 weeks compared with the 8 weeks prior to pretreatment. HI-P (in participants with pretreatment platelet count < 100 × 10⁹/L): Absolute increase in platelets of ≥ 30 × 10⁹/L if pretreatment value > 20 × 10⁹/L or increase from < 20 × 10⁹/L to > 20 × 10⁹/L and by at least 100%. HI-N (in participants with pretreatment neutrophils < 1.0 × 10⁹/L): At least 100% increase in neutrophils and an absolute increase of > 0.5 × 10⁹/L. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Duration of response is defined as the time from the first response morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi)) was observed until relapse, PD, or death based on the IWG 2003 response criteria and central review. If no relapse, PD, or death was observed, the duration of response was censored at the last response assessment date that the participant was known to be progression-free. Response was assessed following every 3 treatment cycles until treatment discontinuation.

Treatment emergent adverse events are adverse events (AEs) that occurred or worsened on or after the first dose of study drug (durvalumab or azacitidine) and within 90 days after last dose of durvalumab or 28 days after last dose of azacitidine. A treatment-related TEAE is a TEAE where the causal relationship was assessed by the investigator as "Suspected". The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death due to AE.

Overall survival is defined as the time between randomization and death/censored date. Participants who were alive at the time of the clinical data cut-off were censored at the last known alive date.

One-year survival is defined as the probability of survival at 1 year from randomization and is represented by the Kaplan-Meier estimate of the percentage of participants alive after 1 year.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.

Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.