Trial Outcomes & Findings for 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) (NCT NCT02775903)

Last Updated: 2023-02-28

Results Overview

Overall response rate (ORR) is defined as the percentage of participants achieving a 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. CR: ≤ 5% myeloblasts in bone marrow (BM), and peripheral blood: hemoglobin ≥ 11 g/dL; platelets ≥ 100 × 10⁹/L; neutrophils ≥ 1.0 × 10⁹/L; blasts 0% PR: BM blasts decreased by ≥ 50% but still \> 5%; peripheral blood as for CR mCR: BM ≤ 5% myeloblasts and decrease by ≥ 50% HI: Any of the following: •Hemoglobin increase by ≥ 1.5 g/dL or reduction of units of red blood cell (RBC) transfusions of at least 4 RBC transfusions/8 weeks compared with pretreatment •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% •At least 100% increase in neutrophils and an absolute increase of \> 0.5 × 10⁹/L

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

213 participants

Primary outcome timeframe

Response was assessed following every 3 treatment cycles until treatment discontinuation; median duration of treatment was 239 days (AZA) and 215 days (DUR) in the AZA + DUR group and 210 days in the AZA alone group.

Results posted on

2023-02-28

Participant Flow

This study consisted of 2 cohorts: • Adults with previously untreated intermediate, high or very high risk myelodysplastic syndromes (MDS) not eligible for hematopoietic stem cell transplantation (HSCT). • Adults with previously untreated acute myeloid leukemia (AML) ≥ 65 years and not eligible for HSCT with intermediate or poor cytogenetic risk.

Within each cohort participants were randomized in a 1:1 ratio to receive either azacitidine plus durvalumab or azacitidine alone. Randomization was stratified according to cytogenetic risk: • Very good, good and intermediate versus poor and very poor for MDS • Intermediate versus poor for AML .

Participant milestones

Participant milestones
Measure	MDS: Azacitidine + Durvalumab Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
Overall Study STARTED	42	42	64	65
Overall Study COMPLETED	4	1	1	5
Overall Study NOT COMPLETED	38	41	63	60

Reasons for withdrawal

Reasons for withdrawal
Measure	MDS: Azacitidine + Durvalumab Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
Overall Study Death	7	11	12	11
Overall Study Adverse Event	0	1	12	3
Overall Study Progressive disease	15	14	30	20
Overall Study Lack of Efficacy	2	2	2	6
Overall Study Withdrawal by Subject	7	5	5	8
Overall Study Other reasons	7	8	2	12

Baseline Characteristics

Data were collected and reported separately for each cohort.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab n=64 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone n=65 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	Total n=213 Participants Total of all reporting groups
Age, Continuous MDS	72.5 years STANDARD_DEVIATION 6.53 • n=42 Participants • Data were collected and reported separately for each cohort.	73.2 years STANDARD_DEVIATION 8.83 • n=42 Participants • Data were collected and reported separately for each cohort.	—	—	72.8 years STANDARD_DEVIATION 7.72 • n=84 Participants • Data were collected and reported separately for each cohort.
Age, Continuous AML	—	—	76.2 years STANDARD_DEVIATION 5.97 • n=64 Participants • Data were collected and reported separately for each cohort.	75.3 years STANDARD_DEVIATION 5.36 • n=65 Participants • Data were collected and reported separately for each cohort.	75.8 years STANDARD_DEVIATION 5.67 • n=129 Participants • Data were collected and reported separately for each cohort.
Age, Customized MDS Cohort · < 65 years	2 Participants n=42 Participants • Data were collected and reported separately for each cohort.	10 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	12 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Age, Customized MDS Cohort · ≥ 65 to < 75 years	21 Participants n=42 Participants • Data were collected and reported separately for each cohort.	11 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	32 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Age, Customized MDS Cohort · ≥ 75 years	19 Participants n=42 Participants • Data were collected and reported separately for each cohort.	21 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	40 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Age, Customized AML Cohort · < 65 years	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Age, Customized AML Cohort · ≥ 65 to < 75 years	—	—	24 Participants n=64 Participants • Data were collected and reported separately for each cohort.	28 Participants n=65 Participants • Data were collected and reported separately for each cohort.	52 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Age, Customized AML Cohort · ≥ 75 years	—	—	40 Participants n=64 Participants • Data were collected and reported separately for each cohort.	37 Participants n=65 Participants • Data were collected and reported separately for each cohort.	77 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Sex: Female, Male MDS Cohort · Female	14 Participants n=42 Participants • Data were collected and reported separately for each cohort.	12 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	26 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Sex: Female, Male MDS Cohort · Male	28 Participants n=42 Participants • Data were collected and reported separately for each cohort.	30 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	58 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Sex: Female, Male AML Cohort · Female	—	—	24 Participants n=64 Participants • Data were collected and reported separately for each cohort.	34 Participants n=65 Participants • Data were collected and reported separately for each cohort.	58 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Sex: Female, Male AML Cohort · Male	—	—	40 Participants n=64 Participants • Data were collected and reported separately for each cohort.	31 Participants n=65 Participants • Data were collected and reported separately for each cohort.	71 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) MDS Cohort · Hispanic or Latino	5 Participants n=42 Participants • Data were collected and reported separately for each cohort.	2 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	7 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) MDS Cohort · Not Hispanic or Latino	30 Participants n=42 Participants • Data were collected and reported separately for each cohort.	33 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	63 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) MDS Cohort · Unknown or Not Reported	7 Participants n=42 Participants • Data were collected and reported separately for each cohort.	7 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	14 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) AML Cohort · Hispanic or Latino	—	—	6 Participants n=64 Participants • Data were collected and reported separately for each cohort.	3 Participants n=65 Participants • Data were collected and reported separately for each cohort.	9 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) AML Cohort · Not Hispanic or Latino	—	—	39 Participants n=64 Participants • Data were collected and reported separately for each cohort.	41 Participants n=65 Participants • Data were collected and reported separately for each cohort.	80 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Ethnicity (NIH/OMB) AML Cohort · Unknown or Not Reported	—	—	19 Participants n=64 Participants • Data were collected and reported separately for each cohort.	21 Participants n=65 Participants • Data were collected and reported separately for each cohort.	40 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · American Indian or Alaska Native	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	0 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · Asian	2 Participants n=42 Participants • Data were collected and reported separately for each cohort.	1 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	3 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · Black or African American	1 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	1 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · Native Hawaiian or Other Pacific Islander	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	0 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · White	30 Participants n=42 Participants • Data were collected and reported separately for each cohort.	33 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	63 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · Not Collected or Reported	7 Participants n=42 Participants • Data were collected and reported separately for each cohort.	5 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	12 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized MDS Cohort · Other	2 Participants n=42 Participants • Data were collected and reported separately for each cohort.	3 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	5 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · American Indian or Alaska Native	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · Asian	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · Black or African American	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	1 Participants n=65 Participants • Data were collected and reported separately for each cohort.	1 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · Native Hawaiian or Other Pacific Islander	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · White	—	—	45 Participants n=64 Participants • Data were collected and reported separately for each cohort.	42 Participants n=65 Participants • Data were collected and reported separately for each cohort.	87 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · Not Collected or Reported	—	—	18 Participants n=64 Participants • Data were collected and reported separately for each cohort.	21 Participants n=65 Participants • Data were collected and reported separately for each cohort.	39 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Race/Ethnicity, Customized AML Cohort · Other	—	—	1 Participants n=64 Participants • Data were collected and reported separately for each cohort.	1 Participants n=65 Participants • Data were collected and reported separately for each cohort.	2 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · 0 - Fully active	17 Participants n=42 Participants • Data were collected and reported separately for each cohort.	18 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	35 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · 1 - Restricted but ambulatory	20 Participants n=42 Participants • Data were collected and reported separately for each cohort.	20 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	40 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · 2 - Ambulatory but unable to work	3 Participants n=42 Participants • Data were collected and reported separately for each cohort.	4 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	7 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · 3 - Limited self-care	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	0 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · 4 - Completely Disabled	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	0 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status MDS Cohort · Missing	2 Participants n=42 Participants • Data were collected and reported separately for each cohort.	0 Participants n=42 Participants • Data were collected and reported separately for each cohort.	—	—	2 Participants n=84 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · 0 - Fully active	—	—	19 Participants n=64 Participants • Data were collected and reported separately for each cohort.	26 Participants n=65 Participants • Data were collected and reported separately for each cohort.	45 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · 1 - Restricted but ambulatory	—	—	40 Participants n=64 Participants • Data were collected and reported separately for each cohort.	32 Participants n=65 Participants • Data were collected and reported separately for each cohort.	72 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · 2 - Ambulatory but unable to work	—	—	5 Participants n=64 Participants • Data were collected and reported separately for each cohort.	7 Participants n=65 Participants • Data were collected and reported separately for each cohort.	12 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · 3 - Limited self-care	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · 4 - Completely Disabled	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Eastern Cooperative Oncology Group (ECOG) Performance Status AML Cohort · Missing	—	—	0 Participants n=64 Participants • Data were collected and reported separately for each cohort.	0 Participants n=65 Participants • Data were collected and reported separately for each cohort.	0 Participants n=129 Participants • Data were collected and reported separately for each cohort.
Revised International Prognostic Scoring System (IPSS-R) Cytogenetic Risk Groups (MDS Cohort) Very good	1 Participants n=42 Participants • Participants in the MDS cohort only	1 Participants n=42 Participants • Participants in the MDS cohort only	—	—	2 Participants n=84 Participants • Participants in the MDS cohort only
Revised International Prognostic Scoring System (IPSS-R) Cytogenetic Risk Groups (MDS Cohort) Good	10 Participants n=42 Participants • Participants in the MDS cohort only	10 Participants n=42 Participants • Participants in the MDS cohort only	—	—	20 Participants n=84 Participants • Participants in the MDS cohort only
Revised International Prognostic Scoring System (IPSS-R) Cytogenetic Risk Groups (MDS Cohort) Intermediate	9 Participants n=42 Participants • Participants in the MDS cohort only	8 Participants n=42 Participants • Participants in the MDS cohort only	—	—	17 Participants n=84 Participants • Participants in the MDS cohort only
Revised International Prognostic Scoring System (IPSS-R) Cytogenetic Risk Groups (MDS Cohort) Poor	8 Participants n=42 Participants • Participants in the MDS cohort only	9 Participants n=42 Participants • Participants in the MDS cohort only	—	—	17 Participants n=84 Participants • Participants in the MDS cohort only
Revised International Prognostic Scoring System (IPSS-R) Cytogenetic Risk Groups (MDS Cohort) Very Poor	14 Participants n=42 Participants • Participants in the MDS cohort only	14 Participants n=42 Participants • Participants in the MDS cohort only	—	—	28 Participants n=84 Participants • Participants in the MDS cohort only
Cytogenetic Risk Classifications (AML Cohort) Better risk	—	—	0 Participants n=64 Participants • Participants in the AML cohort only	0 Participants n=65 Participants • Participants in the AML cohort only	0 Participants n=129 Participants • Participants in the AML cohort only
Cytogenetic Risk Classifications (AML Cohort) Intermediate risk	—	—	25 Participants n=64 Participants • Participants in the AML cohort only	26 Participants n=65 Participants • Participants in the AML cohort only	51 Participants n=129 Participants • Participants in the AML cohort only
Cytogenetic Risk Classifications (AML Cohort) Poor risk	—	—	16 Participants n=64 Participants • Participants in the AML cohort only	16 Participants n=65 Participants • Participants in the AML cohort only	32 Participants n=129 Participants • Participants in the AML cohort only
Cytogenetic Risk Classifications (AML Cohort) Missing	—	—	23 Participants n=64 Participants • Participants in the AML cohort only	23 Participants n=65 Participants • Participants in the AML cohort only	46 Participants n=129 Participants • Participants in the AML cohort only

PRIMARY outcome

Timeframe: Response was assessed following every 3 treatment cycles until treatment discontinuation; median duration of treatment was 239 days (AZA) and 215 days (DUR) in the AZA + DUR group and 210 days in the AZA alone group.

Population: All randomized participants in the MDS cohort; participants who discontinued before 6 cycles of treatment without achieving overall response were counted as non-responders.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Overall Response Rate	61.9 percentage of participants Interval 47.22 to 76.59	47.6 percentage of participants Interval 32.51 to 62.72	—	—

PRIMARY outcome

Timeframe: Response was assessed following every 3 treatment cycles until treatment discontinuation; median duration of treatment was 198 days (AZA) and 171 days (DUR) in the AZA + DUR group and 203 days in the AZA alone group.

Population: All randomized participants in the AML cohort; participants who discontinued before 6 cycles of treatment without achieving overall response were counted as non-responders.

Overall response rate for AML is defined as the percentage of participants achieving an overall response of morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) based on modified IWG 2003 response criteria for AML and central review. CR: 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. CRi: Defined as a morphologic complete remission but the ANC count may be \< 1.0 x10⁹/L and/or the platelet count may be \< 100 x10⁹/L.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=64 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=65 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Overall Response Rate	31.3 percentage of participants Interval 19.89 to 42.61	35.4 percentage of participants Interval 23.76 to 47.01	—	—

SECONDARY outcome

Timeframe: From randomization to the earliest date any response (up to approximately 34 months)

Population: All participants randomized in the MDS cohort

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Kaplan Meier Estimate of Time to First Response	14.3 Weeks Interval 11.3 to 20.9	18.4 Weeks Interval 8.1 to 26.1	—	—

SECONDARY outcome

Timeframe: From randomization to to the date of disease relapse or death from any cause, whichever occurred first (up to approximately 34 months)

Population: Participants randomized in the MDS cohort who had a CR or PR

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=3 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=4 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Kaplan Meier Estimate of Relapse-free Survival	3.7 Months Interval 3.0 to Insufficient number of participants with events	NA Months Interval 0.0 to Insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: From randomization up to approximately 34 months

Population: Participants randomized in the MDS cohort evaluable for cytogenetic response (ie, participants with baseline cytogenetic abnormalities).

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=21 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=23 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Percentage of Participants Who Achieved a Cytogenetic Response	47.6 percentage of participants Interval 26.26 to 68.98	34.8 percentage of participants Interval 15.32 to 54.25	—	—

SECONDARY outcome

Timeframe: From randomization to the first documented progressive disease (PD), relapse, or death due to any cause (up to approximately 34 months)

Population: All participants randomized in the MDS cohort (PFS was a pre-specified secondary outcome measure in the MDS cohort only).

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

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Kaplan-Meier Estimate of Progression-free Survival (PFS)	8.7 Months Interval 5.6 to 10.2	8.6 Months Interval 3.4 to 11.2	—	—

SECONDARY outcome

Timeframe: From randomization to the first overall response, or death (up to approximately 34 months)

Population: Participants randomized in the MDS cohort with an overall response (CR, mCR, PR, or HI)

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=26 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=20 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Kaplan-Meier Estimate of Duration of Response	33.9 Weeks Interval 22.1 to 47.4	39.7 Weeks Interval 26.3 to 73.1	—	—

SECONDARY outcome

Timeframe: From randomization to the date the participant had documented transformation to AML (up to approximately 34 months)

Population: All participants randomized in the MDS cohort.

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Kaplan-Meier Estimate of Time to AML Transformation	20.8 Months Interval 15.0 to Insufficient number of participants with events	27.7 Months Interval 11.3 to Insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: From randomization until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial (up to approximately 34 months)

Population: All participants randomized in the MDS cohort

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
MDS Cohort: Percentage of Participants With Disease Transformation to AML	23.8 Percentage of participants	19.0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: From randomization and the earliest date any response (up to approximately 34 months)

Population: All participants randomized in the AML cohort

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=64 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=65 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Kaplan Meier Estimate of Time to First Response	NA Weeks Interval 14.3 to Insufficient number of participants with events.	25.3 Weeks Interval 13.9 to 43.0	—	—

SECONDARY outcome

Timeframe: From randomization to the date of disease relapse or death from any cause, whichever occurred first (up to approximately 34 months)

Population: Participants randomized in the AML cohort with a response (CR or CRi)

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=20 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=23 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Kaplan Meier Estimate of Relapse-free Survival	9.5 Months Interval 5.0 to 15.0	12.2 Months Interval 3.5 to 19.3	—	—

SECONDARY outcome

Timeframe: From randomization up to approximately 34 months)

Population: Participants randomized in the AML cohort evaluable for cytogenetic response (ie participants with baseline cytogenetic abnormalities).

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=53 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=50 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Percentage of Participants Who Achieved a Complete Cytogenetic Response	11.3 Percentage of participants Interval 2.79 to 19.85	16.0 Percentage of participants Interval 5.84 to 26.16	—	—

SECONDARY outcome

Timeframe: From randomization up to approximately 34 months

Population: All participants randomized in the AML cohort (the percentage of participants with hematologic improvement was a pre-specified secondary endpoint for the AML cohort only).

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=64 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=65 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Percentage of Participants With Hematologic Improvement	42.2 Percentage of participants Interval 30.09 to 54.29	38.5 Percentage of participants Interval 26.63 to 50.29	—	—

SECONDARY outcome

Timeframe: From randomization until relapse, PD, or death (up to approximately 34 months)

Population: Participants randomized in the AML cohort with an objective response (CR or CRi)

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=20 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=23 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
AML Cohort: Kaplan-Meier Estimate of Duration of Response	24.6 Weeks Interval 16.4 to 48.0	52.0 Weeks Interval 15.1 to 84.0	—	—

SECONDARY outcome

Timeframe: From first dose to 90 days after last dose of durvalumab or 28 days after last dose of azacitidine proir to the extension study (up to approximately 34 months)

Population: All participants who received at least 1 dose of any study drug.

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=38 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=41 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab n=64 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone n=62 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any treatment-emergent adverse event (TEAE)	38 Participants	41 Participants	64 Participants	62 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE related to DUR	27 Participants	—	50 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE related to AZA	31 Participants	33 Participants	56 Participants	50 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE related to DUR or AZA	35 Participants	33 Participants	58 Participants	50 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3 TEAE	36 Participants	30 Participants	60 Participants	50 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3 TEAE related to DUR	18 Participants	—	29 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3 TEAE related to AZA	18 Participants	16 Participants	32 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 3 TEAE related to DUR or AZA	22 Participants	16 Participants	38 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 4 TEAE	33 Participants	27 Participants	43 Participants	34 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 4 TEAE related to DUR	16 Participants	—	18 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 4 TEAE related to AZA	19 Participants	15 Participants	27 Participants	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 4 TEAE related to DUR or AZA	22 Participants	15 Participants	28 Participants	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 5 TEAE	10 Participants	9 Participants	26 Participants	11 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 5 TEAE related to DUR	2 Participants	—	1 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 5 TEAE related to AZA	1 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Grade 5 TEAE related to DUR or AZA	2 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious TEAE	34 Participants	29 Participants	56 Participants	45 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious TEAE related to DUR	11 Participants	—	33 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious TEAE related to AZA	9 Participants	10 Participants	25 Participants	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious TEAE related to DUR or AZA	14 Participants	10 Participants	34 Participants	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of DUR	5 Participants	—	21 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of AZA	0 Participants	1 Participants	13 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of DUR or AZA	5 Participants	1 Participants	22 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose reduction of AZA	3 Participants	6 Participants	10 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose interruption of DUR	24 Participants	—	34 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose interruption of AZA	27 Participants	19 Participants	39 Participants	32 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to dose interruption of DUR or AZA	28 Participants	19 Participants	41 Participants	32 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to ongoing DUR infusion interruption	2 Participants	—	2 Participants	—

SECONDARY outcome

Timeframe: From randomization to date of death or last known alive date (up to approximately 34 months)

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab n=64 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone n=65 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
Kaplan-Meier Estimate of Overall Survival	11.6 Months Interval 9.5 to Insufficient number of participants with events	16.3 Months Interval 9.8 to 22.6	13.0 Months Interval 10.3 to 17.3	14.4 Months Interval 10.0 to 16.6

SECONDARY outcome

Timeframe: At 12 months after randomization

Population: All randomized participants

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.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=42 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab n=64 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone n=65 Participants Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
One-year Survival	49 Percentage of participants	58 Percentage of participants	52 Percentage of participants	55 Percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 end of infusion (EOI), Cycle 2 Day 1 pre-infusion, Cycle 4 Day 1 pre-infusion and EOI, and Cycle 6 Day 1 pre-infusion

Population: Participants who received at least one dose of durvalumab and who had at least 1 measurable durvalumab concentration value and with available data at each time point.

Outcome measures

Outcome measures
Measure	MDS: Azacitidine + Durvalumab n=38 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	MDS: Azacitidine Alone n=62 Participants Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine + Durvalumab Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.	AML: Azacitidine Alone Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
Durvalumab Serum Concentration Cycle 1 Day 1 end of infusion	375548.511 ng/mL Standard Deviation 140777.0558	378598.369 ng/mL Standard Deviation 201902.4363	—	—
Durvalumab Serum Concentration Cycle 2 Day 1 pre-infusion	84380.032 ng/mL Standard Deviation 92174.3455	54216.956 ng/mL Standard Deviation 28336.3692	—	—
Durvalumab Serum Concentration Cycle 4 Day 1 pre-infusion	132266.794 ng/mL Standard Deviation 126971.6223	78622.429 ng/mL Standard Deviation 41708.9956	—	—
Durvalumab Serum Concentration Cycle 4 Day 1 end of infusion	433942.600 ng/mL Standard Deviation 233241.0329	391523.395 ng/mL Standard Deviation 147928.1261	—	—
Durvalumab Serum Concentration Cycle 6 Day 1 pre-infusion	114448.977 ng/mL Standard Deviation 64608.9007	142517.871 ng/mL Standard Deviation 248212.8037	—	—

SECONDARY outcome

Timeframe: Baseline and last lab measurement collected in Cycle 2 (Last measurement could be taken either on Day 1, 8, 15 or 22)