Trial Outcomes & Findings for A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients (NCT NCT02367456)

Last Updated: 2024-01-19

Results Overview

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

73 participants

Primary outcome timeframe

maximum of approximately 15 months

Results posted on

2024-01-19

Participant Flow

12 participants were enrolled and received combination therapy of glasdegib and azacitidine in the Lead-in Cohort (LIC). 31 participants were enrolled in the acute myeloid leukemia (AML) cohort, and 30 received glasdegib + azacitidine (1 participant withdrew consent before receiving treatment). 30 participants were enrolled and received glasdegib + azacitidine in the myelodysplastic syndrome (MDS) cohort.

Participant milestones

Participant milestones
Measure	Lead-in Cohort Participants received subcutaneous (SC) administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg once daily (QD). In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit drug-drug interaction (DDI) evaluation.	AML Cohort Participants received SC or intravenous (IV) administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Study STARTED	12	30	30
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	12	30	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Lead-in Cohort Participants received subcutaneous (SC) administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg once daily (QD). In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit drug-drug interaction (DDI) evaluation.	AML Cohort Participants received SC or intravenous (IV) administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Overall Study Death	8	24	17
Overall Study Lost to Follow-up	1	3	1
Overall Study Other reason	3	3	9
Overall Study Study Participation Terminated by Sponsor	0	0	3

Baseline Characteristics

A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	AML Cohort n=30 Participants Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.	Total n=72 Participants Total of all reporting groups
Age, Customized <18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized 18-44 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized 45-64 years	3 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants
Age, Customized >=65 years	9 Participants n=5 Participants	27 Participants n=7 Participants	23 Participants n=5 Participants	59 Participants n=4 Participants
Age, Customized <75 years	7 Participants n=5 Participants	16 Participants n=7 Participants	22 Participants n=5 Participants	45 Participants n=4 Participants
Age, Customized >=75 years	5 Participants n=5 Participants	14 Participants n=7 Participants	8 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	12 Participants n=7 Participants	6 Participants n=5 Participants	23 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants	49 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants	58 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	22 Participants n=7 Participants	24 Participants n=5 Participants	57 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: maximum of approximately 15 months

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) All-causality TEAEs	12 Participants	—	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) Treatment-related TEAEs	12 Participants	—	—
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Lead-in Cohort (LIC) Maximum Grade 3 or 4 TEAEs	8 Participants	—	—

PRIMARY outcome

Timeframe: maximum of approximately 15 months

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.

A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Serious Adverse Events (SAEs) in the LIC All-causality SAEs	9 Participants	—	—
Number of Participants With Serious Adverse Events (SAEs) in the LIC Treatment-related SAEs	7 Participants	—	—

PRIMARY outcome

Timeframe: maximum of approximately 16 months

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment. Number of participants analyzed = number of participants evaluable for this outcome measure (OM). Number analyzed = number of participants evaluable for this OM with at least 1 result of the specified laboratory parameter.

Hematology lab parameters included activated partial thromboplastin time, hemoglobin, prothrombin international normalized ratio, lymphocyte, neutrophil, platelet, white blood cell; chemistry parameters included alanine aminotransferase, aspartate aminotransferase, alkaline aminotransferase, blood bilirubin, creatine phosphokinase, creatinine, calcium, blood glucose, potassium, magnesium, sodium, albumin, phosphate. Grades of lab abnormalities were defined by NCI 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 instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. Grade 1-4 results are reported.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Laboratory Abnormalities in the LIC Activated partial thromboplastin time prolonged	5 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Neutrophil count decreased	10 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Aspartate aminotransferase increased	2 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC creatine phosphokinase increased	0 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypoalbuminemia	5 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Anemia	12 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hemoglobin increased	0 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC international normalized ratio increased	8 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Lymphocyte count decreased	9 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Lymphocyte count increased	3 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Platelet count decreased	12 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC White blood cell decreased	11 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Alanine aminotransferase increased	4 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Alkaline phosphatase increase	0 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Blood bilirubin increased	6 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Creatinine increased	11 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypercalcemia	1 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hyperglycemia	1 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hyperkalemia	3 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypermagnesemia	2 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypernatremia	1 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypocalcemia	3 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypoglycemia	1 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypokalemia	3 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypomagnesemia	2 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hyponatremia	6 Participants	—	—
Number of Participants With Laboratory Abnormalities in the LIC Hypophosphatemia	4 Participants	—	—

PRIMARY outcome

Timeframe: maximum of 23 months in AML cohort and 34 months in MDS cohort

Population: The full analysis population included all participants who received at least 1 dose of any study treatment.

Percentage of participants achieving CR as defined by the 2017 European Leukemia Net (ELN) Response Criteria for all participants with AML and modified International Working Group (IWG) criteria (2006) for all participants with MDS in the expansion cohorts. For AML cohort, CR was defined as neutrophils ≥ 1 x 10\^9/L, platelets ≥ 1 x 10\^11/L, percentage of bone marrow blasts (BMB) \<5% with no peripheral blasts and no blasts with Auer rods, no extramedullary disease (EMD), and transfusion independent. For MDS cohort, CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10\^9/L, platelets ≥1 x 10\^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Percentage of Participants Achieving Complete Remission (CR) in the AML and MDS Cohorts	20.0 Percentage of participants Interval 7.7 to 38.6	13.3 Percentage of participants Interval 3.8 to 30.7	—

SECONDARY outcome

Timeframe: maximum of approximately 16 months

Population: The safety analysis population included all participants who received at least 1 dose of study treatment.

Response rate (Percentage of participants achieving CR + PR among all the enrolled and treated patients) as defined by modified International Working Group (IWG) criteria (2006) in the LIC. CR was defined as having responses of hemoglobin ≥11 g/dL, neutrophils ≥1 x 10\^9/L, platelets ≥1 x 10\^11/L, percentage of blasts = 0%, percentage of BMB≤5%, and normal maturation of all cell lines (note if has persistent dysplasia), and all responses must last at least 4 weeks. PR was defined as meeting all CR criteria if abnormal before treatment except BMB, percentage of BMB decreased by ≥50% but still \>5% for at least 4 weeks.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Percentage of Participants Achieving Complete Remission (CR) + Partial Remission (PR) in the LIC	25.0 Percentage of participants	—	—

SECONDARY outcome

Timeframe: maximum of approximately 16 months

Population: The full analysis set was defined as all participants who received at least 1 dose of any study treatment.

Number of participants with efficacy measures other than CR as defined by modified IWG criteria (2006) in LIC, including marrow CR(mCR), stable disease(SD), hematologic improvement(HI). CR: hemoglobin≥11 g/dL, neutrophils≥1 x 10\^9/L, platelets≥1 x 10\^11/L, percentage of blasts=0%, percentage of BMB≤5%, normal maturation of all cell lines (note if has persistent dysplasia), all responses last at least 4 weeks. mCR: BMB≤5% \& decreased by≥50%. SD: failure to achieve PR, no evidence of progression. HI: erythroid response (pretreatment\<11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment\<1x10\^11/L): increase of≥30x10\^9/L if starting with \>20x10\^9/L, and increase from \<20x10\^9/L to \>20x10\^9/L and by at least 100%; neutrophil response (pretreatment\<1x10\^9/L): at least a 100% increase, absolute increase \>0.5x10\^9/L

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Efficacy Measures Other Than CR in the LIC marrow CR	2 Participants	—	—
Number of Participants With Efficacy Measures Other Than CR in the LIC stable disease	4 Participants	—	—
Number of Participants With Efficacy Measures Other Than CR in the LIC hematologic improvement of at least 1 lineage	6 Participants	—	—

SECONDARY outcome

Timeframe: maximum of around 23 months in AML cohort and 40 months in MDS cohort

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. TEAEs were AEs that occurred after initiation of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. Grades of AEs were defined by NCI CTCAE version 4.03.Grade 1=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With TEAEs in the AML and MDS Cohorts All-causality TEAEs	30 Participants	30 Participants	—
Number of Participants With TEAEs in the AML and MDS Cohorts Treatment-related TEAEs	29 Participants	29 Participants	—
Number of Participants With TEAEs in the AML and MDS Cohorts Maximum Grade 3 or 4 TEAEs	20 Participants	25 Participants	—

SECONDARY outcome

Timeframe: maximum of around 23 months in AML cohort and 40 months in MDS cohort

Population: The safety analysis population included all participants who received at least 1 dose of study treatment

An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With SAEs in the AML and MDS Cohorts All-causality SAEs	24 Participants	19 Participants	—
Number of Participants With SAEs in the AML and MDS Cohorts Treatment-related SAEs	8 Participants	9 Participants	—

SECONDARY outcome

Timeframe: maximum of around 23 months in AML cohort and 40 months in MDS cohort

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment. Number of Participants Analyzed = number of participants evaluable for this outcome measure. Number Analyzed = number of participants with at least 1 observation of the given lab test.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Lymphocyte count decreased	23 Participants	24 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Platelet count decreased	29 Participants	26 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts White blood cell decreased	22 Participants	27 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypokalemia	8 Participants	3 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Activated partial thromboplastin time prolonged	0 Participants	0 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Anemia	30 Participants	29 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hemoglobin increased	0 Participants	0 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts international normalized ratio increased	0 Participants	2 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Leukocytosis	0 Participants	1 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Lymphocyte count increased	6 Participants	2 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Neutrophil count decreased	25 Participants	25 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Alanine aminotransferase increased	13 Participants	12 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Alkaline phosphatase increased	7 Participants	8 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Aspartate aminotransferase increased	11 Participants	9 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Blood bilirubin increased	3 Participants	10 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts creatine phosphokinase increased	5 Participants	4 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts creatinine increased	29 Participants	28 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypercalcemia	3 Participants	0 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hyperglycemia	3 Participants	4 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hyperkalemia	6 Participants	6 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypermagnesemia	1 Participants	2 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypernatremia	2 Participants	1 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypoalbuminemia	22 Participants	19 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypocalcemia	3 Participants	11 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypoglycemia	4 Participants	3 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypomagnesemia	12 Participants	10 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hyponatremia	18 Participants	12 Participants	—
Number of Participants With Laboratory Abnormalities in the AML and MDS Cohorts Hypophosphatemia	13 Participants	7 Participants	—

SECONDARY outcome

Timeframe: maximum of 23 months

Population: The full analysis population included all participants who received at least 1 dose of any study treatment.

Number of participants with partial hematologic recovery (CRh), CR with incomplete blood count recovery (CRi), partial remission (PR), stable disease (SD), and morphologic leukemia free state (MLFS). CRh: neutrophils\>5x10\^8/L, platelets\>5x10\^10/L, BMB\<5%, no peripheral blasts, no blasts with Auer rods, no extramedullary disease (EMD), not qualifying for CR. CRi: neutrophils \<1x10\^9/L or platelets\<1x10\^11/L; BMB \<5%, no peripheral blasts, no blasts with Auer rods; no EMD; neutrophils or platelets not recovered; not qualifying for CRh. PR: neutrophils ≥1x10\^9/L; platelets ≥1x10\^11/L; blasts decreased to 5-25% and ≥50% decrease from pretreatment; blasts≤5% if Auer rod positive. SD: ≥3 months of absence of CR without minimal residual disease (CRMRD-), CR, CRh, CRi, PR, and MLFS, criteria for PD not met. MLFS: neutrophils \<1x10\^9/L and platelets\<1x10\^11/L, BMB\<5%, no blasts with Auer rods; no EMD; neutrophils and platelets not recovered; not qualifying for CRi

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort partial hematologic recovery (CRh)	0 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort CR with incomplete blood count recovery (CRi)	1 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort partial remission (PR)	2 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort morphologic leukemia free state (MLFS)	1 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the AML Cohort stable disease (SD)	6 Participants	—	—

SECONDARY outcome

Timeframe: maximum of 34 months

Population: The full analysis population included all participants who received at least 1 dose of any study treatment.

Number of participants with PR, mCR, SD, complete or partial cytogenetic response, and HI. PR: BMB \>5% and decreased by ≥50% (at least 4 weeks), meeting all CR criteria if abnormal before treatment except BMB. mCR: BMB ≤5% and decreased by ≥50%. SD: failure to achieve PR, no evidence of progression. Complete or partial cytogenic response: disappearance of chromosomal abnormality without new ones, or ≥ 50% reduction of chromosomal abnormality. HI: erythroid response (pretreatment \<11g/dL): hemoglobin increase by≥1.5 g/dL, relevant reduction of units of red blood cell transfusions by at least 4 transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks; platelet response (pretreatment \<1x10\^11/L): increase of ≥30x10\^9/L if starting with \>20x10\^9/L, and increase from \<20x10\^9/L to \>20x10\^9/L and by at least 100%; neutrophil response (pretreatment \<1x10\^9/L): at least a 100% increase, absolute increase \>0.5x10\^9/L.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort PR	3 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort mCR	5 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort SD	8 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort Complete cytogenetic response	5 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort Partial cytogenetic response	1 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort HI of at least 1 lineage	9 Participants	—	—
Number of Participants With Disease-Specific Efficacy Measures in the MDS Cohort HI of at least 1 lineage without CR or PR	3 Participants	—	—

SECONDARY outcome

Timeframe: maximum of approximately 32 months in AML cohort and 32 months in MDS cohort

Population: The full analysis population included all participants who received at least 1 dose of any study treatment.

Overall survival (OS) was defined as the time from date of first study treatment to date of death from any cause. Patients last known to be alive were to be censored at the date of last contact. OS was analyzed and displayed graphically for each expansion cohort separately using the Kaplan-Meier method. The median event time and corresponding two-sided 95%CI were provided for each cohort. OS was first analyzed when the primary endpoint of CR was analyzed in the respective expansion cohort.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Kaplan-Meier Estimate of Median Overall Survival (OS) in the AML and MDS Cohorts	9.2 Months Interval 6.2 to 14.0	17.8 Months Interval 9.3 to The upper limit was not estimable due to insufficient number of participants with events.	—

SECONDARY outcome

Timeframe: maximum of 23 months in AML cohort and 34 months in MDS cohort

Population: The analysis population included all participants who received at least 1 dose of any study treatment.

Duration of CR was defined as the duration from date of first achieving CR to the date of disease progression (relapse) after CR, or death due to any cause. Participants last known to be alive who were free from disease progression or relapse after CR were censored at the date of the last assessment that verified their disease status. Duration of CR was analyzed using the Kaplan-Meier method. Disease progression was defined as: percentage of bone marrow blasts increased by ≥50% to \>5% (for participants with \<5% blasts at screening), \>10% (for participants with 5-10% blasts at screening), \>20% (for participants with 11-20% blasts at screening) or \>30% (for participants with 21-30% blasts at screening), and with any of the following condition: at least 50% decrease from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by ≥2 g/dL; transfusion dependence.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Duration of CR in the AML and MDS Cohorts	5.78 Months Interval 0.03 to 16.85	6.18 Months Interval 0.72 to 18.07	—

SECONDARY outcome

Timeframe: maximum of 23 months in AML cohort and 34 months in MDS cohort

Population: The analysis population included all participants who received at least 1 dose of any study treatment.

Time to CR was defined for participants in the expansion cohorts who had achieved response on study as the time from date of the first dose of study drug to date of the first documentation of response. Time to CR was analyzed using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Time to CR in the AML and MDS Cohorts	5.54 Months Interval 3.12 to 5.98	4.39 Months Interval 3.71 to 5.55	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Cycle 1 Day 15

Population: The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available. Number of participants analyzed = number of participants evaluable for this OM. Number analyzed = number of participants with evaluable results at the specific timepoint.

Maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D7	1013 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58	—	—
Maximum Plasma Concentration (Cmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D15	991.4 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 57	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Cycle 1 Day 15

Population: The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest. Number of participants analyzed = number of participants evaluable for this OM. Number analyzed = number of participants with evaluable results at the specific timepoint.

Area under the plasma concentration curve from time zero to end of dosing interval (AUCtau) of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D7	13230 nanogram * hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 49	—	—
Area Under the Plasma Concentration Curve From Time Zero to End of Dosing Interval (AUCtau) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D15	14350 nanogram * hour/milliliter (ng*hr/mL) Geometric Coefficient of Variation 61	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 1, 4, 6, 24 hours post-dose on Cycle 1 Day 7 and Cycle 1 Day 15

Time to first occurrence of maximum plasma concentration of glasdegib dosed in combination with azacitidine (C1D7) and when dosed alone (C1D15) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D7	1.050 hour Interval 1.0 to 5.7	—	—
Time to First Occurrence of Maximum Plasma Concentration (Tmax) of Glasdegib Dosed in Combination With Azacitidine (C1D7) and When Dosed Alone (C1D15) in the Lead-in Cohort C1D15	1.500 hour Interval 1.0 to 6.02	—	—

SECONDARY outcome

Timeframe: 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1, predose and 0.25, 0.5, 1, 2, 6 hours postdose on Cycle 1 Day 7

Population: The PK concentration analysis set included all participants who received treatment and had at least 1 value of analyte concentration of glasdegib or azacitidine available.

Maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Cmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D1	778.5 ng/mL Geometric Coefficient of Variation 23	—	—
Cmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D7	716.9 ng/mL Geometric Coefficient of Variation 32	—	—

SECONDARY outcome

Timeframe: 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1, predose and 0.25, 0.5, 1, 2, 6 hours postdose on Cycle 1 Day 7

Population: The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.

Area under the plasma concentration curve from time zero to extrapolated infinite time of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D1	1319 ng*hr/mL Geometric Coefficient of Variation 19	—	—
Area Under the Plasma Concentration Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D7	1260 ng*hr/mL Geometric Coefficient of Variation 21	—	—

SECONDARY outcome

Timeframe: 0.25, 0.5, 1, 2, 6 hours post-dose on Cycle 1 Day 1, predose and 0.25, 0.5, 1, 2, 6 hours postdose on Cycle 1 Day 7

Population: The PK parameter analysis set included all participants who received study treatment and had at least 1 of the PK parameters of interest.

Time to first occurrence of maximum plasma concentration of azacitidine dosed in combination with glasdegib (C1D7) and when dosed alone (C1D1) in the Lead-in Cohort was estimated using non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D1	0.5000 hour Interval 0.0 to 1.0	—	—
Tmax of Azacitidine Dosed in Combination With Glasdegib (C1D7) and When Dosed Alone (C1D1) in the Lead-in Cohort C1D7	0.5000 hour Interval 0.25 to 1.08	—	—

SECONDARY outcome

Timeframe: Pre-dose and 1 and 4 hours post-dose on Cycle 1 Day 15 (C1D15) and Cycle 2 Day 1 (C2D1)

Trough plasma concentration was defined as the estimated lowest concentration before next dose administration.

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=30 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Trough Plasma Concentration (Ctrough) of Glasdegib on Cycle 1 Day 15 and Cycle 2 Day 1 in the AML and MDS Cohorts C1D15	468.440 ng/mL Geometric Coefficient of Variation 88	308.144 ng/mL Geometric Coefficient of Variation 95	—
Trough Plasma Concentration (Ctrough) of Glasdegib on Cycle 1 Day 15 and Cycle 2 Day 1 in the AML and MDS Cohorts C2D1	462.806 ng/mL Geometric Coefficient of Variation 110	167.483 ng/mL Geometric Coefficient of Variation 52	—

SECONDARY outcome

Timeframe: maximum of approximately 15 months in the LIC cohort, 23 months in AML cohort, and 40 months in MDS cohort

Population: The safety analysis population included all participants who received at least 1 dose of any study treatment.

Number of participants that met categorical criteria of QTcF values in LIC, AML and MDS cohorts

Outcome measures

Outcome measures
Measure	Lead-in Cohort n=12 Participants Participants received SC administration of azacitidine daily at a dose of 75 mg/m2/day on Days 1-7 of every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD. In Cycle 1 only, administration of glasdegib commenced on Day 2 of the cycle (C1D2) to permit DDI evaluation.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine with a starting dose of 75 mg/m2/day for 7 days every 28 days, and received daily oral administration of glasdegib at home with a starting dose of 100 mg QD.	MDS Cohort n=30 Participants Participants received SC or IV administration of azacitidine at the starting dose of 75 mg/m2/day for 7 days every 28 days, and received oral self-administration of glasdegib daily and continuously at home with a starting dose of 100 mg QD.
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts Maximum QTcF interval <450 ms	5 Participants	16 Participants	17 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts 450 ms <=Maximum QTcF interval <480 ms	2 Participants	6 Participants	7 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts 480 ms <=Maximum QTcF interval <500 ms	4 Participants	5 Participants	4 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts Maximum QTcF interval ≥500 ms	1 Participants	3 Participants	2 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts QTcF maximum increase from baseline <30 ms	3 Participants	18 Participants	21 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts 30 ms <= QTcF maximum increase from baseline <60 ms	7 Participants	10 Participants	7 Participants
Number of Participants Meeting Categorical Criteria of QTcF Values in LIC, AML and MDS Cohorts QTcF maximum increase from baseline >=60 ms	2 Participants	2 Participants	2 Participants

Adverse Events

Lead-in Cohort

Serious events: 9 serious events

Other events: 12 other events

Deaths: 9 deaths

AML Cohort

Serious events: 24 serious events

Other events: 29 other events

Deaths: 25 deaths

MDS Cohort

Serious events: 19 serious events

Other events: 29 other events

Deaths: 17 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 8007181021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER