ENTO in AML: Entospletinib Monotherapy and in Combination With Chemotherapy in Adults With Acute Myeloid Leukemia (AML)

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02343939
• Collaborator: (none)
• Enrollment: 148
• Locations: 17
• Arms: 3
• Actual Duration (Months): 43.7
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy, safety, and tolerability of entospletinib when administered as monotherapy or in combination with chemotherapy in adults with acute myeloid leukemia (AML).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Entospletinib; Drug: Daunorubicin; Drug: Cytarabine; Drug: Decitabine; Drug: Azacitidine	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Sep 4, 2018
• Actual Study Completion Date: Feb 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Entospletinib + daunorubicin + cytarabine (Group A) Dose Escalation: Entospletinib up to 400 mg for 14 days and then entospletinib up to 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Dose Expansion: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Some participants will have the option to receive post-induction therapy with entospletinib 400 mg in combination with cytarabine/cytosine arabinoside (ARA-C). Participants may receive maintenance therapy with 28-day cycles of entospletinib 400 mg for up to twelve 28-day cycles, if the participant is not eligible for stem cell transplant.	Drug: Entospletinib; Tablet(s) administered orally every 12 hours; Other Names: GS-9973 ENTO ; Drug: Daunorubicin; 60 mg/m^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles; Drug: Cytarabine; 100 mg/m^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles
Experimental: Entospletinib + decitabine (Group B) Dose Escalation: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with decitabine for 10 days beginning on Day 1 of every 28-day cycle (at least 2 cycles of induction therapy but no more than 4 cycles). Participants who are intolerant of decitabine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles. Dose Expansion: Entospletinib 400 mg for 14 days for the safety run-in participants or Entospletinib 400 mg for 5 days for the randomization participants. Then entospletinib 400 mg in combination with decitabine or azacitidine (at least 2 cycles of induction therapy but no more than 4 cycles). Some participants will have the option to receive maintenance therapy with entospletinib in combination with decitabine or azacitidine. Participants who are intolerant of decitabine or azacitidine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles.	Drug: Entospletinib; Tablet(s) administered orally every 12 hours; Other Names: GS-9973 ENTO ; Drug: Decitabine; 20 mg/m^2 administered intravenously; Drug: Azacitidine; 75 mg/m^2 administered intravenously or subcutaneously
Experimental: Entospletinib (Group C) Dose Escalation: Entospletinib up to 800 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the study protocol. Dose Expansion: Entospletinib 400 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the protocol.	Drug: Entospletinib; Tablet(s) administered orally every 12 hours; Other Names: GS-9973 ENTO

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [Group A: Cycle 0 Day 1 to Cycle 2 Day 28; Group B: Cycle 0 Day 1 to Cycle 1 Day 28; Group C: Cycle 1 Day 1 to Cycle 1 Day 28 (Cycle length: for Cycle 0 = 14 days, for all other cycles = 28 days)]

   DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLT assessment was applicable only for Phase 1b and Phase 2 safety run-in participants.

2. Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction [At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)]

   Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Morphologic CR included CR and cytogenetic CR (CRc). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/microliter (mcL); Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis.

3. Percentage of Participants With Composite Complete Remission at the End of Induction [At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)]

   Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Composite complete remission included CR, CRc, and morphologic complete remission with incomplete blood count recovery (CRi). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets.

4. Percentage of Participants With Overall Response at the End of Induction [At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)]

   Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Overall response included CR, CRc, CRi, and partial remission (PR). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets. PR required all of the following: ≥ 50% decrease in blasts in bone marrow aspirate to a range of 5% to 25%; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; Independent of transfusions; and A value of ≤ 5% blasts was also considered a PR if Auer rods were detected.

Secondary Outcome Measures

1. Duration of Exposure of Entospletinib [First dose date up to approximately 3 years]

2. Event Free Survival (EFS) [First dose date up to approximately 38 months]

   EFS was defined as the time interval from the start of the study therapy until the date of treatment failure, acute myeloid leukemia (AML) relapse, or death from any cause, whichever occurred first. Participants who received other anti-cancer therapy (prior to the event if any) were censored. Median EFS was analyzed using Kaplan-Meier (KM) method.

3. Overall Survival (OS) [First dose date up to approximately 38 months]

   OS was defined as the time interval from the start of the study therapy to death from any cause. Median OS was analyzed using KM method.

4. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [First dose date up to the last dose date plus 30 days (maximum: 18 months)]

5. Percentage of Participants Who Experienced Laboratory Abnormalities [First dose date up to the last dose date plus 30 days (maximum: 18 months)]

   Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Adults with AML in need of treatment

• Group A : Individuals ≥ 18 years of age with previously untreated AML by World Health Organization (WHO) criteria who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician

• Group B: Individuals > 70 years of age with previously untreated AML by WHO criteria; or individuals ≤ 70 years of age with previously untreated AML who refuse or are unable to receive chemotherapy with 7+3 as determined by the treating physician

• Group C: Individuals ≥ 18 years of age with relapsed/refractory AML by WHO criteria; or with relapsed/refractory AML with mixed-lineage leukemia (MLL); or with previously untreated AML by WHO criteria and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive chemotherapy and hypomethylating agent as determined by the treating physician

Key Exclusion Criteria:

• Known active central nervous system or leptomeningeal lymphoma

• Subjects with acute promyelocytic leukemia (M3)

• Treatment with proton pump inhibitors (PPIs) within 7 days prior to enrollment.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States
2	University of Chicago	Chicago	Illinois	United States
3	Loyola University Medical Center	Maywood	Illinois	United States
4	Indiana University	Indianapolis	Indiana	United States
5	University of Kansas Medical Center Research Institute, Inc	Fairway	Kansas	United States
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States
7	Henry Ford Health System	Detroit	Michigan	United States
8	Karmanos Cancer Institute	Detroit	Michigan	United States
9	Weill Cornell Medical College - New York - Presbyterian Hospital	New York	New York	United States
10	Duke Cancer Center	Durham	North Carolina	United States
11	University Hospitals Case Medical Center	Cleveland	Ohio	United States
12	Ohio State University	Columbus	Ohio	United States
13	Oregon Health & Science University	Portland	Oregon	United States	97239
14	Saint Francis Cancer Center	Greenville	South Carolina	United States
15	Princess Margaret	Toronto	Ontario	Canada
16	Jewish General Hospital	Montreal	Quebec	Canada
17	Universitätsklinikum Frankfurt Medizinische Klinik II	Frankfurt		Germany	60590

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Feb 15, 2018
• Statistical Analysis Plan - Jun 19, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02343939
• Other Study ID Numbers: GS-US-339-1559; 2016-003353-16
• First Posted: Jan 22, 2015
• Last Update Posted: Nov 15, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Azacitidine; Decitabine; Daunorubicin

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in United States, Canada, and Germany. The first participant was screened on 01 July 2015.
Pre-assignment Detail	233 participants were screened.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Period Title: Overall Study
STARTED	3	50	5	6	8	17	15	37	7
COMPLETED	0	2	0	0	0	0	0	0	0
NOT COMPLETED	3	48	5	6	8	17	15	37	7

Baseline Characteristics

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Total
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Total of all reporting groups
Overall Participants	3	50	5	6	8	17	14	35	7	145
Age, Customized (Count of Participants)
< 65 Years	3 100%	32 64%	0 0%	1 16.7%	1 12.5%	1 5.9%	0 0%	17 48.6%	0 0%	55 37.9%
≥ 65 years	0 0%	18 36%	5 100%	5 83.3%	7 87.5%	16 94.1%	14 100%	18 51.4%	7 100%	90 62.1%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	21 42%	2 40%	2 33.3%	2 25%	7 41.2%	3 21.4%	18 51.4%	5 71.4%	61 42.1%
Male	2 66.7%	29 58%	3 60%	4 66.7%	6 75%	10 58.8%	11 78.6%	17 48.6%	2 28.6%	84 57.9%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	0 0%	2 4%	0 0%	0 0%	0 0%	0 0%	0 0%	2 5.7%	0 0%	4 2.8%
Not Hispanic or Latino	3 100%	48 96%	5 100%	6 100%	7 87.5%	15 88.2%	13 92.9%	33 94.3%	7 100%	137 94.5%
Not Permitted	0 0%	0 0%	0 0%	0 0%	1 12.5%	2 11.8%	1 7.1%	0 0%	0 0%	4 2.8%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	3 100%	44 88%	3 60%	6 100%	6 75%	14 82.4%	11 78.6%	31 88.6%	7 100%	125 86.2%
Black or African American	0 0%	5 10%	2 40%	0 0%	1 12.5%	0 0%	1 7.1%	2 5.7%	0 0%	11 7.6%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.9%	0 0%	1 0.7%
Other	0 0%	1 2%	0 0%	0 0%	0 0%	0 0%	1 7.1%	1 2.9%	0 0%	3 2.1%
Not Permitted	0 0%	0 0%	0 0%	0 0%	1 12.5%	3 17.6%	1 7.1%	0 0%	0 0%	5 3.4%
Region of Enrollment (Count of Participants)
Canada	0 0%	4 8%	0 0%	0 0%	0 0%	0 0%	0 0%	6 17.1%	0 0%	10 6.9%
United States	3 100%	46 92%	5 100%	6 100%	8 100%	15 88.2%	11 78.6%	29 82.9%	7 100%	130 89.7%
Germany	0 0%	0 0%	0 0%	0 0%	0 0%	2 11.8%	3 21.4%	0 0%	0 0%	5 3.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Description	DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLT assessment was applicable only for Phase 1b and Phase 2 safety run-in participants.
Time Frame	Group A: Cycle 0 Day 1 to Cycle 2 Day 28; Group B: Cycle 0 Day 1 to Cycle 1 Day 28; Group C: Cycle 1 Day 1 to Cycle 1 Day 28 (Cycle length: for Cycle 0 = 14 days, for all other cycles = 28 days)

Outcome Measure Data

Analysis Population Description

The DLT Analysis Set included all participants who received 21 days of ENTO (applicable to all groups) and all doses of cytarabine and daunorubicin in Group A Phase 1b, decitabine in Group B Phase 1b, or azacitidine in Group B Phase 2 safety run-in during the DLT assessment window; or experienced a DLT during the DLT assessment window.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	6	3	6	6	6	6
Number [percentage of participants]	0 0%	0 0%	0 0%	16.7 278.3%	0 0%	0 0%	16.7 119.3%

2. Primary Outcome

Title	Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction
Description	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Morphologic CR included CR and cytogenetic CR (CRc). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/microliter (mcL); Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis.
Time Frame	At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all participants who received at least 1 dose of study drug with treatment designated according to the planned treatment.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML)	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL)	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML)
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants R/R AML with mixed-lineage leukemia (MLL) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with previously untreated AML who were unfit for chemotherapy or hypomethylating agents or refused chemotherapy or hypomethylating agent received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	9	41	5	6	8	17	14	7	7	6	13	9
Number (95% Confidence Interval) [percentage of participants]	66.7 2223.3%	66.7 133.4%	46.3 926%	0.0 0%	16.7 208.8%	25.0 147.1%	0.0 0%	7.1 20.3%	0.0 0%	0.0 0%	0.0 NaN	15.4 NaN	11.1 NaN

3. Primary Outcome

Title	Percentage of Participants With Composite Complete Remission at the End of Induction
Description	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Composite complete remission included CR, CRc, and morphologic complete remission with incomplete blood count recovery (CRi). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets.
Time Frame	At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML)	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL)	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML)
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants R/R AML with mixed-lineage leukemia (MLL) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with previously untreated AML who were unfit for chemotherapy or hypomethylating agents or refused chemotherapy or hypomethylating agent received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	9	41	5	6	8	17	14	7	7	6	13	9
Number (95% Confidence Interval) [percentage of participants]	100.0 3333.3%	77.8 155.6%	65.9 1318%	40.0 666.7%	50.0 625%	25.0 147.1%	23.5 167.9%	14.3 40.9%	14.3 204.3%	0.0 0%	0.0 NaN	15.4 NaN	11.1 NaN

4. Primary Outcome

Title	Percentage of Participants With Overall Response at the End of Induction
Description	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Overall response included CR, CRc, CRi, and partial remission (PR). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets. PR required all of the following: ≥ 50% decrease in blasts in bone marrow aspirate to a range of 5% to 25%; Neutrophils ≥ 1,000/mcL; Platelets ≥ 100,000/mcL; Independent of transfusions; and A value of ≤ 5% blasts was also considered a PR if Auer rods were detected.
Time Frame	At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML)	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL)	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML)
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants R/R AML with mixed-lineage leukemia (MLL) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with previously untreated AML who were unfit for chemotherapy or hypomethylating agents or refused chemotherapy or hypomethylating agent received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	9	41	5	6	8	17	14	7	7	6	13	9
Number (95% Confidence Interval) [percentage of participants]	100.0 3333.3%	77.8 155.6%	70.7 1414%	40.0 666.7%	50.0 625%	25.0 147.1%	23.5 167.9%	14.3 40.9%	14.3 204.3%	0.0 0%	0.0 NaN	15.4 NaN	11.1 NaN

5. Secondary Outcome

Title	Duration of Exposure of Entospletinib
Time Frame	First dose date up to approximately 3 years

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	50	5	6	8	17	14	35	7
Median (Full Range) [weeks]	8.6	7.1	13.7	15.4	10.1	13.9	10.1	4.4	7.6

6. Secondary Outcome

Title	Event Free Survival (EFS)
Description	EFS was defined as the time interval from the start of the study therapy until the date of treatment failure, acute myeloid leukemia (AML) relapse, or death from any cause, whichever occurred first. Participants who received other anti-cancer therapy (prior to the event if any) were censored. Median EFS was analyzed using Kaplan-Meier (KM) method.
Time Frame	First dose date up to approximately 38 months

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML)	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL)	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML)
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants R/R AML with mixed-lineage leukemia (MLL) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with previously untreated AML who were unfit for chemotherapy or hypomethylating agents or refused chemotherapy or hypomethylating agent received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	9	41	5	6	8	17	14	7	7	6	13	9
Median (95% Confidence Interval) [months]	NA	1.9	9.0	2.2	2.9	2.3	3.2	2.4	1.8	1.8	1.0	1.0	1.7

7. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time interval from the start of the study therapy to death from any cause. Median OS was analyzed using KM method.
Time Frame	First dose date up to approximately 38 months

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b ENTO 400 mg	Group C Phase 1b ENTO 800 mg	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML)	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL)	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML)
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants R/R AML with mixed-lineage leukemia (MLL) received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants with previously untreated AML who were unfit for chemotherapy or hypomethylating agents or refused chemotherapy or hypomethylating agent received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	9	41	5	6	8	17	14	7	7	6	13	9
Median (95% Confidence Interval) [months]	37.1	34.1	NA	3.2	5.3	6.9	7.3	6.2	5.9	5.6	8.2	7.9	2.2

8. Secondary Outcome

Title	Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame	First dose date up to the last dose date plus 30 days (maximum: 18 months)

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	50	5	6	8	17	14	35	7
Number [percentage of participants]	100.0 3333.3%	100.0 200%	100.0 2000%	100.0 1666.7%	100.0 1250%	100.0 588.2%	100.0 714.3%	100.0 285.7%	100.0 1428.6%

9. Secondary Outcome

Title	Percentage of Participants Who Experienced Laboratory Abnormalities
Description	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.
Time Frame	First dose date up to the last dose date plus 30 days (maximum: 18 months)

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set who had non-missing postbaseline value prior to or on the last dosing date plus 30 days were analyzed.

Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	Group B Phase 1b ENTO 200 mg + Decitabine	Group B Phase 1b ENTO 400 mg + Decitabine	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	Group C Phase 1b/2 ENTO 400 mg	Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).	Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.	Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.	Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
Measure Participants	3	50	5	6	7	17	14	35	7
Any Laboratory Abnormality	100 3333.3%	100 200%	100 2000%	100 1666.7%	100 1250%	94.1 553.5%	100 714.3%	100 285.7%	100 1428.6%
Grade 3 or 4 Laboratory Abnormalities	100 3333.3%	98.0 196%	100 2000%	100 1666.7%	85.7 1071.3%	94.1 553.5%	92.9 663.6%	82.9 236.9%	85.7 1224.3%

Adverse Events

Time Frame	- All-Cause Mortality: First dose date up to approximately 38 months. - Adverse Events: First dose date up to the last dose date plus 30 days (maximum: 18 months)
Adverse Event Reporting Description	The Safety Analysis Set included all participants who received at least 1 dose of study drug.
Arm/Group Title	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin		Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin		Group B Phase 1b ENTO 200 mg + Decitabine		Group B Phase 1b ENTO 400 mg + Decitabine		Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)		Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)		Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)		Group C Phase 1b/2 ENTO 400 mg		Group C Phase 1b ENTO 800 mg
Arm/Group Description	Participants received ENTO 200 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (during induction chemotherapy).		Phase1b/2: Participants received ENTO 400 mg tablet orally every 12 hours on Days 1 to 14 (Cycle 0) (monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with chemotherapy (cytarabine 100 mg/m^2 on Days 1-7 and daunorubicin 60 mg/m^2 on Days 1-3 intravenously) for up to two 14-day cycles (Cycles 1 and 2) (induction chemotherapy). Phase 2 only: Participants who achieved a CR/CRi and did not require or could not proceed to allogeneic stem cell transplantation (SCT) were offered post-remission chemotherapy (cytarabine 3 g/m^2 intravenously every 12 hours on Days 1, 3, and 5 or 1 g/m^2 intravenously once daily on Days 1-5) in combination with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for at least 3 and up to 4 cycles. Participants who maintained a CR/CRi after 3 or 4 cycles were offered maintenance therapy with ENTO 400 mg tablet orally every 12 hours on Days 1-28 of each 28-day cycle for up to 12 cycles.		Participants received ENTO 200 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 200 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 200 mg as monotherapy after completing 2 maintenance cycles.		Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28) (induction chemotherapy). Participants who achieved a CR/CRi received SCT (if eligible) per investigator's discretion; other participants were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.		As part of the safety run-in, participants received ENTO 400 mg tablet orally every 12 hours on Days 1-14 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of a 28-day cycle (Cycle 1). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.		Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with decitabine 20 mg/m^2 intravenously on Days 1-10 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with decitabine on Days 1-5 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to decitabine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.		Participants were randomized to receive ENTO 400 mg tablet orally every 12 hours on Days 1-5 (Cycle 0) (during monotherapy lead-in), followed by ENTO 400 mg tablet orally every 12 hours in combination with azacitidine 75 mg/m^2 intravenously on Days 1-7 of every 28-day cycle for 2 cycles (or up to 4 cycles for participants with persistent disease after Cycle 2 Day 28). Participants who were not eligible for SCT were offered maintenance therapy with ENTO every 12 hours on Days 1-28 in combination with azacitidine on Days 1-7 of every 28-day cycle for at least 2 cycles (maximum up to 12 cycles). Participants who were intolerant to azacitidine were offered maintenance therapy with ENTO 400 mg as monotherapy after completing 2 maintenance cycles.		Participants received ENTO 400 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.		Participants received ENTO 800 mg tablet orally every 12 hours on Days 1-28 of every 28-day cycle until treatment failure, start of new therapy, unacceptable toxicity, withdrawal of consent, withdrawal from study by investigator, or study termination by sponsor.
All Cause Mortality
	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin		Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin		Group B Phase 1b ENTO 200 mg + Decitabine		Group B Phase 1b ENTO 400 mg + Decitabine		Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)		Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)		Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)		Group C Phase 1b/2 ENTO 400 mg		Group C Phase 1b ENTO 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		21/50 (42%)		5/5 (100%)		4/6 (66.7%)		5/8 (62.5%)		12/17 (70.6%)		11/14 (78.6%)		30/35 (85.7%)		6/7 (85.7%)
Serious Adverse Events
	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin		Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin		Group B Phase 1b ENTO 200 mg + Decitabine		Group B Phase 1b ENTO 400 mg + Decitabine		Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)		Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)		Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)		Group C Phase 1b/2 ENTO 400 mg		Group C Phase 1b ENTO 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		23/50 (46%)		5/5 (100%)		5/6 (83.3%)		7/8 (87.5%)		11/17 (64.7%)		7/14 (50%)		19/35 (54.3%)		4/7 (57.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/3 (0%)		13/50 (26%)		4/5 (80%)		4/6 (66.7%)		3/8 (37.5%)		8/17 (47.1%)		0/14 (0%)		5/35 (14.3%)		0/7 (0%)
Cardiac disorders
Angina pectoris	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Atrial fibrillation	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Cardiac arrest	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Cardiac failure chronic	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Cardiac failure congestive	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Sinus bradycardia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Gastrointestinal disorders
Colitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Constipation	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		1/7 (14.3%)
Gastric haemorrhage	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Gastrointestinal haemorrhage	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Haematemesis	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Haematochezia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Intestinal ischaemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Large intestine perforation	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Oesophagitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Proctalgia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Stomatitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Vomiting	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
General disorders
Asthenia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Catheter site haemorrhage	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Non-cardiac chest pain	0/3 (0%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pyrexia	0/3 (0%)		1/50 (2%)		1/5 (20%)		1/6 (16.7%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Infections and infestations
Anal abscess	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Bacteraemia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Bacterial infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Cellulitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Cellulitis staphylococcal	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Clostridium difficile colitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Device related infection	0/3 (0%)		1/50 (2%)		0/5 (0%)		2/6 (33.3%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Enteritis infectious	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Escherichia sepsis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Fungal infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Influenza	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Lung infection	0/3 (0%)		0/50 (0%)		2/5 (40%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		2/7 (28.6%)
Mucosal infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Otitis media	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Pneumonia	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		2/14 (14.3%)		2/35 (5.7%)		0/7 (0%)
Sepsis	0/3 (0%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		2/8 (25%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Staphylococcal infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Staphylococcal sepsis	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Urinary tract infection	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Vascular device infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Fall	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Investigations
Blood alkaline phosphatase increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Transaminases increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Troponin I increased	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Metabolism and nutrition disorders
Dehydration	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		1/7 (14.3%)
Gout	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hyponatraemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Tumour lysis syndrome	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Thyroid cancer	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Nervous system disorders
Cerebrovascular accident	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Cognitive disorder	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Haemorrhage intracranial	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Neuromyopathy	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Transient ischaemic attack	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Renal and urinary disorders
Acute kidney injury	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/3 (0%)		1/50 (2%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Haemoptysis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Hypoxia	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Lung consolidation	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Pleural effusion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pneumonitis	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pneumothorax	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Respiratory failure	0/3 (0%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Rash maculo-papular	0/3 (0%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Skin haemorrhage	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Vascular disorders
Deep vein thrombosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Hypotension	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Thrombosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin		Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin		Group B Phase 1b ENTO 200 mg + Decitabine		Group B Phase 1b ENTO 400 mg + Decitabine		Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)		Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)		Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)		Group C Phase 1b/2 ENTO 400 mg		Group C Phase 1b ENTO 800 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		50/50 (100%)		5/5 (100%)		6/6 (100%)		7/8 (87.5%)		17/17 (100%)		14/14 (100%)		33/35 (94.3%)		7/7 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		24/50 (48%)		3/5 (60%)		1/6 (16.7%)		2/8 (25%)		5/17 (29.4%)		6/14 (42.9%)		10/35 (28.6%)		3/7 (42.9%)
Febrile neutropenia	2/3 (66.7%)		36/50 (72%)		1/5 (20%)		3/6 (50%)		2/8 (25%)		2/17 (11.8%)		4/14 (28.6%)		8/35 (22.9%)		0/7 (0%)
Leukocytosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Lymphadenopathy	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Neutropenia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pancytopenia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Thrombocytopenia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Cardiac disorders
Angina pectoris	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Arrhythmia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Atrial fibrillation	0/3 (0%)		7/50 (14%)		1/5 (20%)		0/6 (0%)		1/8 (12.5%)		3/17 (17.6%)		3/14 (21.4%)		1/35 (2.9%)		0/7 (0%)
Bradycardia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Diastolic dysfunction	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Palpitations	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Sinus bradycardia	0/3 (0%)		5/50 (10%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Sinus tachycardia	0/3 (0%)		6/50 (12%)		0/5 (0%)		2/6 (33.3%)		1/8 (12.5%)		2/17 (11.8%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Supraventricular tachycardia	0/3 (0%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Tachycardia	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		2/14 (14.3%)		0/35 (0%)		0/7 (0%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Hypoacusis	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Tinnitus	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Eye disorders
Dry eye	1/3 (33.3%)		4/50 (8%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Eye haemorrhage	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Eye oedema	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Eye pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Lacrimation increased	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Optic nerve cupping	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Periorbital oedema	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Scleral hyperaemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Ulcerative keratitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Vision blurred	0/3 (0%)		10/50 (20%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Gastrointestinal disorders
Abdominal distension	0/3 (0%)		7/50 (14%)		0/5 (0%)		2/6 (33.3%)		0/8 (0%)		0/17 (0%)		2/14 (14.3%)		2/35 (5.7%)		1/7 (14.3%)
Abdominal pain	1/3 (33.3%)		13/50 (26%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		4/14 (28.6%)		4/35 (11.4%)		0/7 (0%)
Abdominal pain lower	0/3 (0%)		1/50 (2%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Abdominal pain upper	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		4/17 (23.5%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Anal incontinence	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Anal ulcer	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Angina bullosa haemorrhagica	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Ascites	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Colitis	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Colitis ischaemic	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Constipation	1/3 (33.3%)		20/50 (40%)		3/5 (60%)		4/6 (66.7%)		6/8 (75%)		10/17 (58.8%)		9/14 (64.3%)		3/35 (8.6%)		0/7 (0%)
Diarrhoea	1/3 (33.3%)		34/50 (68%)		1/5 (20%)		3/6 (50%)		3/8 (37.5%)		9/17 (52.9%)		4/14 (28.6%)		14/35 (40%)		4/7 (57.1%)
Dry mouth	0/3 (0%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Dyspepsia	0/3 (0%)		8/50 (16%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Dysphagia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		1/17 (5.9%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Enterocolitis	1/3 (33.3%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Faecaloma	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Flatulence	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Gastrooesophageal reflux disease	1/3 (33.3%)		6/50 (12%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Gingival bleeding	0/3 (0%)		1/50 (2%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Haemorrhoidal haemorrhage	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Haemorrhoids	0/3 (0%)		5/50 (10%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		3/17 (17.6%)		1/14 (7.1%)		3/35 (8.6%)		0/7 (0%)
Hiatus hernia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Ileus	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Intestinal dilatation	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Intra-abdominal haematoma	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Lip pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Lower gastrointestinal haemorrhage	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Mouth haemorrhage	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Mouth ulceration	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Nausea	3/3 (100%)		34/50 (68%)		4/5 (80%)		4/6 (66.7%)		4/8 (50%)		5/17 (29.4%)		7/14 (50%)		15/35 (42.9%)		2/7 (28.6%)
Oral pain	0/3 (0%)		5/50 (10%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Pancreatic disorder	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Proctalgia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		3/14 (21.4%)		0/35 (0%)		0/7 (0%)
Rectal haemorrhage	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		2/14 (14.3%)		0/35 (0%)		0/7 (0%)
Regurgitation	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Salivary hypersecretion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Small intestinal obstruction	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Stomatitis	0/3 (0%)		8/50 (16%)		1/5 (20%)		1/6 (16.7%)		0/8 (0%)		4/17 (23.5%)		1/14 (7.1%)		6/35 (17.1%)		1/7 (14.3%)
Tongue ulceration	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Vomiting	2/3 (66.7%)		16/50 (32%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		6/17 (35.3%)		5/14 (35.7%)		8/35 (22.9%)		1/7 (14.3%)
General disorders
Asthenia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Catheter site dermatitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Catheter site erythema	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Catheter site pain	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Catheter site rash	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Chest pain	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		2/14 (14.3%)		2/35 (5.7%)		0/7 (0%)
Chills	0/3 (0%)		8/50 (16%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		5/14 (35.7%)		4/35 (11.4%)		0/7 (0%)
Device related thrombosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Face oedema	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Fatigue	1/3 (33.3%)		14/50 (28%)		3/5 (60%)		1/6 (16.7%)		2/8 (25%)		9/17 (52.9%)		6/14 (42.9%)		10/35 (28.6%)		3/7 (42.9%)
Feeling hot	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
General physical health deterioration	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Injection site erythema	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		2/14 (14.3%)		0/35 (0%)		0/7 (0%)
Injection site pain	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Malaise	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Mucosal inflammation	0/3 (0%)		10/50 (20%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		4/35 (11.4%)		0/7 (0%)
Non-cardiac chest pain	0/3 (0%)		7/50 (14%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Oedema	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Oedema peripheral	2/3 (66.7%)		29/50 (58%)		2/5 (40%)		3/6 (50%)		4/8 (50%)		6/17 (35.3%)		4/14 (28.6%)		4/35 (11.4%)		3/7 (42.9%)
Pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Performance status decreased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pyrexia	0/3 (0%)		9/50 (18%)		0/5 (0%)		2/6 (33.3%)		2/8 (25%)		2/17 (11.8%)		1/14 (7.1%)		5/35 (14.3%)		0/7 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Infections and infestations
Abdominal infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Atypical pneumonia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Bacteraemia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Bacterial infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Bacterial sepsis	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Candida infection	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Cellulitis	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Chronic sinusitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Clostridium difficile colitis	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Clostridium difficile infection	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Corona virus infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Device related infection	1/3 (33.3%)		9/50 (18%)		1/5 (20%)		2/6 (33.3%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Enterococcal bacteraemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Folliculitis	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Leptotrichia infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Lung infection	0/3 (0%)		11/50 (22%)		1/5 (20%)		2/6 (33.3%)		1/8 (12.5%)		1/17 (5.9%)		0/14 (0%)		3/35 (8.6%)		0/7 (0%)
Mucosal infection	0/3 (0%)		3/50 (6%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Mycobacterium avium complex infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Oral candidiasis	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Otitis externa	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Perirectal abscess	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pharyngitis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Pneumonia	0/3 (0%)		5/50 (10%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		3/35 (8.6%)		0/7 (0%)
Postoperative wound infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Sepsis	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Sinusitis	0/3 (0%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Skin infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Soft tissue infection	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Staphylococcal infection	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Staphylococcal skin infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Tinea cruris	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Tooth abscess	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Upper respiratory tract infection	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Urinary tract infection	0/3 (0%)		4/50 (8%)		1/5 (20%)		1/6 (16.7%)		3/8 (37.5%)		0/17 (0%)		3/14 (21.4%)		3/35 (8.6%)		0/7 (0%)
Injury, poisoning and procedural complications
Contusion	0/3 (0%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		4/35 (11.4%)		1/7 (14.3%)
Eye contusion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Fall	0/3 (0%)		6/50 (12%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		4/17 (23.5%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Infusion related reaction	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Limb injury	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pelvic fracture	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Skin abrasion	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Transfusion reaction	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Vascular access complication	1/3 (33.3%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Investigations
Activated partial thromboplastin time prolonged	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		2/14 (14.3%)		0/35 (0%)		0/7 (0%)
Alanine aminotransferase increased	0/3 (0%)		8/50 (16%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		0/17 (0%)		1/14 (7.1%)		4/35 (11.4%)		2/7 (28.6%)
Amylase increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		4/14 (28.6%)		0/35 (0%)		0/7 (0%)
Aspartate aminotransferase increased	0/3 (0%)		8/50 (16%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		1/17 (5.9%)		2/14 (14.3%)		3/35 (8.6%)		1/7 (14.3%)
Bilirubin conjugated increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Blood alkaline phosphatase increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		1/14 (7.1%)		2/35 (5.7%)		1/7 (14.3%)
Blood bilirubin increased	0/3 (0%)		12/50 (24%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		5/17 (29.4%)		4/14 (28.6%)		3/35 (8.6%)		0/7 (0%)
Blood creatine phosphokinase increased	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Blood creatinine decreased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Blood creatinine increased	0/3 (0%)		6/50 (12%)		1/5 (20%)		1/6 (16.7%)		1/8 (12.5%)		1/17 (5.9%)		7/14 (50%)		2/35 (5.7%)		2/7 (28.6%)
Blood lactate dehydrogenase increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Blood phosphorus increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Body temperature increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
C-reactive protein increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Chest X-ray abnormal	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Ejection fraction decreased	0/3 (0%)		5/50 (10%)		0/5 (0%)		1/6 (16.7%)		2/8 (25%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Electrocardiogram QT prolonged	0/3 (0%)		4/50 (8%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
International normalised ratio increased	1/3 (33.3%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Lipase increased	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Lymphocyte count decreased	0/3 (0%)		2/50 (4%)		1/5 (20%)		1/6 (16.7%)		2/8 (25%)		4/17 (23.5%)		0/14 (0%)		1/35 (2.9%)		1/7 (14.3%)
Lymphocyte count increased	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Neutrophil count decreased	0/3 (0%)		16/50 (32%)		2/5 (40%)		2/6 (33.3%)		2/8 (25%)		4/17 (23.5%)		2/14 (14.3%)		6/35 (17.1%)		2/7 (28.6%)
Platelet count decreased	0/3 (0%)		26/50 (52%)		3/5 (60%)		3/6 (50%)		3/8 (37.5%)		5/17 (29.4%)		7/14 (50%)		9/35 (25.7%)		1/7 (14.3%)
Spleen palpable	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Troponin I increased	0/3 (0%)		2/50 (4%)		2/5 (40%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Troponin increased	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Ultrasound liver abnormal	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Weight decreased	1/3 (33.3%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Weight increased	2/3 (66.7%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
White blood cell count decreased	0/3 (0%)		18/50 (36%)		2/5 (40%)		1/6 (16.7%)		2/8 (25%)		7/17 (41.2%)		5/14 (35.7%)		4/35 (11.4%)		1/7 (14.3%)
White blood cell count increased	0/3 (0%)		1/50 (2%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		2/35 (5.7%)		0/7 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		22/50 (44%)		2/5 (40%)		1/6 (16.7%)		3/8 (37.5%)		6/17 (35.3%)		6/14 (42.9%)		7/35 (20%)		1/7 (14.3%)
Dehydration	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		2/17 (11.8%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Fluid overload	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hypercalcaemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Hyperglycaemia	0/3 (0%)		2/50 (4%)		1/5 (20%)		1/6 (16.7%)		1/8 (12.5%)		1/17 (5.9%)		2/14 (14.3%)		1/35 (2.9%)		1/7 (14.3%)
Hyperkalaemia	0/3 (0%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		5/14 (35.7%)		0/35 (0%)		0/7 (0%)
Hypermagnesaemia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		4/14 (28.6%)		1/35 (2.9%)		0/7 (0%)
Hypernatraemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Hyperphosphataemia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		1/17 (5.9%)		2/14 (14.3%)		0/35 (0%)		0/7 (0%)
Hyperuricaemia	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		3/14 (21.4%)		1/35 (2.9%)		1/7 (14.3%)
Hypervolaemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hypoalbuminaemia	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		3/14 (21.4%)		1/35 (2.9%)		0/7 (0%)
Hypocalcaemia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		3/17 (17.6%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Hypoglycaemia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		0/35 (0%)		1/7 (14.3%)
Hypokalaemia	0/3 (0%)		10/50 (20%)		1/5 (20%)		0/6 (0%)		1/8 (12.5%)		3/17 (17.6%)		3/14 (21.4%)		4/35 (11.4%)		1/7 (14.3%)
Hypomagnesaemia	0/3 (0%)		7/50 (14%)		1/5 (20%)		0/6 (0%)		1/8 (12.5%)		2/17 (11.8%)		4/14 (28.6%)		3/35 (8.6%)		1/7 (14.3%)
Hyponatraemia	0/3 (0%)		4/50 (8%)		1/5 (20%)		1/6 (16.7%)		0/8 (0%)		4/17 (23.5%)		5/14 (35.7%)		2/35 (5.7%)		0/7 (0%)
Hypophagia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hypophosphataemia	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		4/35 (11.4%)		1/7 (14.3%)
Metabolic acidosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Vitamin D deficiency	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		7/50 (14%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Back pain	1/3 (33.3%)		6/50 (12%)		0/5 (0%)		2/6 (33.3%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		6/35 (17.1%)		1/7 (14.3%)
Bone pain	0/3 (0%)		4/50 (8%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Flank pain	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Groin pain	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Muscular weakness	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Musculoskeletal discomfort	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Musculoskeletal pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Myalgia	0/3 (0%)		6/50 (12%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		4/35 (11.4%)		0/7 (0%)
Myositis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pain in extremity	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		4/17 (23.5%)		1/14 (7.1%)		3/35 (8.6%)		1/7 (14.3%)
Vertebral lesion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Nervous system disorders
Amnesia	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Cerebrovascular accident	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Depressed level of consciousness	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Dizziness	0/3 (0%)		14/50 (28%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		5/35 (14.3%)		0/7 (0%)
Dysgeusia	0/3 (0%)		11/50 (22%)		0/5 (0%)		1/6 (16.7%)		3/8 (37.5%)		2/17 (11.8%)		3/14 (21.4%)		0/35 (0%)		0/7 (0%)
Encephalopathy	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Headache	1/3 (33.3%)		20/50 (40%)		2/5 (40%)		3/6 (50%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		6/35 (17.1%)		2/7 (28.6%)
Lethargy	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Neuropathy peripheral	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Paraesthesia	0/3 (0%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		3/35 (8.6%)		0/7 (0%)
Parosmia	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Somnolence	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Syncope	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Tremor	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Psychiatric disorders
Anxiety	0/3 (0%)		7/50 (14%)		1/5 (20%)		2/6 (33.3%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		3/35 (8.6%)		0/7 (0%)
Apathy	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Confusional state	0/3 (0%)		5/50 (10%)		1/5 (20%)		0/6 (0%)		1/8 (12.5%)		2/17 (11.8%)		0/14 (0%)		2/35 (5.7%)		1/7 (14.3%)
Delirium	0/3 (0%)		3/50 (6%)		0/5 (0%)		2/6 (33.3%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Depression	0/3 (0%)		5/50 (10%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Hallucination	1/3 (33.3%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Insomnia	0/3 (0%)		16/50 (32%)		2/5 (40%)		1/6 (16.7%)		1/8 (12.5%)		2/17 (11.8%)		4/14 (28.6%)		7/35 (20%)		0/7 (0%)
Mental status changes	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		2/17 (11.8%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Restlessness	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Suicidal ideation	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Renal and urinary disorders
Acute kidney injury	0/3 (0%)		8/50 (16%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		2/17 (11.8%)		3/14 (21.4%)		3/35 (8.6%)		0/7 (0%)
Dysuria	0/3 (0%)		1/50 (2%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Haematuria	0/3 (0%)		5/50 (10%)		2/5 (40%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Micturition urgency	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		1/7 (14.3%)
Nephrolithiasis	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pollakiuria	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Renal cyst	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Urinary incontinence	0/3 (0%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Urinary retention	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		1/8 (12.5%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Reproductive system and breast disorders
Scrotal oedema	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Cough	0/3 (0%)		18/50 (36%)		1/5 (20%)		4/6 (66.7%)		3/8 (37.5%)		5/17 (29.4%)		5/14 (35.7%)		5/35 (14.3%)		0/7 (0%)
Dyspnoea	0/3 (0%)		20/50 (40%)		2/5 (40%)		3/6 (50%)		2/8 (25%)		5/17 (29.4%)		4/14 (28.6%)		10/35 (28.6%)		1/7 (14.3%)
Dyspnoea exertional	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		1/7 (14.3%)
Epistaxis	0/3 (0%)		10/50 (20%)		1/5 (20%)		2/6 (33.3%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		7/35 (20%)		0/7 (0%)
Haemoptysis	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hiccups	0/3 (0%)		0/50 (0%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hypoxia	0/3 (0%)		11/50 (22%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Lung infiltration	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Nasal congestion	0/3 (0%)		7/50 (14%)		1/5 (20%)		1/6 (16.7%)		0/8 (0%)		2/17 (11.8%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Oropharyngeal pain	0/3 (0%)		10/50 (20%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		1/14 (7.1%)		2/35 (5.7%)		0/7 (0%)
Paranasal sinus hyposecretion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pleural effusion	0/3 (0%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		3/17 (17.6%)		2/14 (14.3%)		1/35 (2.9%)		0/7 (0%)
Productive cough	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		2/14 (14.3%)		2/35 (5.7%)		0/7 (0%)
Pulmonary hypertension	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Pulmonary oedema	0/3 (0%)		3/50 (6%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Rales	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Respiratory failure	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Rhinitis allergic	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		3/35 (8.6%)		0/7 (0%)
Rhinorrhoea	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Rhonchi	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Sinus pain	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Sleep apnoea syndrome	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Upper respiratory tract congestion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Upper-airway cough syndrome	0/3 (0%)		2/50 (4%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Wheezing	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		6/50 (12%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Dermal cyst	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Drug eruption	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Dry skin	0/3 (0%)		3/50 (6%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Ecchymosis	0/3 (0%)		0/50 (0%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Erythema	1/3 (33.3%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hyperhidrosis	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Night sweats	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Pain of skin	1/3 (33.3%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Petechiae	1/3 (33.3%)		4/50 (8%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		2/14 (14.3%)		2/35 (5.7%)		0/7 (0%)
Photosensitivity reaction	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Pruritus	1/3 (33.3%)		7/50 (14%)		0/5 (0%)		1/6 (16.7%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Rash	0/3 (0%)		3/50 (6%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		2/17 (11.8%)		1/14 (7.1%)		1/35 (2.9%)		0/7 (0%)
Rash macular	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		1/35 (2.9%)		0/7 (0%)
Rash maculo-papular	1/3 (33.3%)		21/50 (42%)		1/5 (20%)		3/6 (50%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		8/35 (22.9%)		1/7 (14.3%)
Rash papular	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Skin lesion	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Skin ulcer	0/3 (0%)		5/50 (10%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		1/14 (7.1%)		0/35 (0%)		0/7 (0%)
Vascular disorders
Deep vein thrombosis	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Embolism	0/3 (0%)		2/50 (4%)		1/5 (20%)		0/6 (0%)		0/8 (0%)		0/17 (0%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Haematoma	0/3 (0%)		1/50 (2%)		0/5 (0%)		0/6 (0%)		1/8 (12.5%)		2/17 (11.8%)		0/14 (0%)		2/35 (5.7%)		0/7 (0%)
Hot flush	0/3 (0%)		0/50 (0%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)
Hypertension	0/3 (0%)		12/50 (24%)		0/5 (0%)		3/6 (50%)		0/8 (0%)		3/17 (17.6%)		0/14 (0%)		2/35 (5.7%)		1/7 (14.3%)
Hypotension	1/3 (33.3%)		7/50 (14%)		0/5 (0%)		0/6 (0%)		2/8 (25%)		4/17 (23.5%)		5/14 (35.7%)		6/35 (17.1%)		1/7 (14.3%)
Orthostatic hypotension	0/3 (0%)		2/50 (4%)		0/5 (0%)		0/6 (0%)		0/8 (0%)		1/17 (5.9%)		0/14 (0%)		0/35 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years