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Phase 1/2 Study of Enasidenib (AG-221) in Adults With Advanced Hematologic Malignancies With an Isocitrate Dehydrogenase Isoform 2 (IDH2) Mutation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01915498
Recruitment Status : Active, not recruiting
First Posted : August 5, 2013
Results First Posted : October 23, 2020
Last Update Posted : October 23, 2020
Sponsor:
Collaborator:
Agios Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hematologic Neoplasms
Intervention Drug: Enasidenib
Enrollment 345
Recruitment Details

Participants were enrolled at 21 sites in France and the United States. The study includes 3 parts: Phase 1 dose escalation, Phase 1 expansion, and Phase 2 expansion.

The primary analysis for efficacy was conducted with a cut-off date of 1 September 2017; safety analyses for ongoing participants continued through 29 July 2019.

Pre-assignment Details In Phase 1 Dose Escalation participants enrolled into sequential cohorts of increasing doses of enasidenib. After the recommended dose was determined enrollment into Phase 1 Expansion and Phase 2 began. Phase 1 Expansion enrolled participants into 4 non-randomized arms. Phase 2 enrolled participants with relapsed/refractory acute myeloid leukemia.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 30 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg BID Phase 1 Dose Escalation: Enasidenib 75 mg BID Phase 1 Dose Escalation: Enasidenib 100 mg BID Phase 1 Dose Escalation: Enasidenib 150 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg QD Phase 1 Dose Escalation: Enasidenib 75 mg QD Phase 1 Dose Escalation: Enasidenib 100 mg QD Phase 1 Dose Escalation: Enasidenib 150 mg QD Phase 1 Dose Escalation: Enasidenib 200 mg QD Phase 1 Dose Escalation: Enasidenib 300 mg QD Phase 1 Dose Escalation: Enasidenib 450 mg QD Phase 1 Dose Escalation: Enasidenib 650 mg QD Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD Phase 2: Enasidenib 100 mg QD Safety Follow-Up: Enasidenib
Hide Arm/Group Description Participants received enasidenib 30 mg tablets twice a day (BID) on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 50 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 75 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 150 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 50 mg tablets once a day (QD) on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 75 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 150 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 200 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 300 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 450 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 650 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants ≥ 60 years old with relapsed, refractory (R/R) AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants remaining on treatment as of the 01 September 2017 data cut-off date continued to receive enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Period Title: Main Analysis (Sept 2013 - Sept 2017)
Started 7 7 7 8 5 9 7 22 6 14 9 5 7 49 25 25 27 106 0
Completed [1] 0 0 0 0 0 0 0 1 0 0 0 1 0 3 0 2 3 6 0
Not Completed 7 7 7 8 5 9 7 21 6 14 9 4 7 46 25 23 24 100 0
Reason Not Completed
Withdrawal by Subject             0             0             0             1             1             0             0             0             0             1             0             0             1             5             1             2             2             5             0
Adverse Event             2             0             1             1             0             0             1             4             1             2             1             1             2             4             1             4             2             16             0
Disease Progression             1             3             3             4             2             5             5             15             4             7             3             2             3             24             14             9             8             41             0
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0
Death             2             1             1             1             1             2             0             1             0             0             2             0             0             4             1             4             3             16             0
Protocol Violation             0             0             0             0             1             0             0             0             0             1             0             0             0             0             0             0             0             0             0
Miscellaneous             0             1             2             0             0             0             0             1             1             1             0             1             0             1             0             1             4             8             0
Bone Marrow Transplant (BMT)             1             2             0             1             0             0             1             0             0             0             1             0             1             6             5             2             2             9             0
Development of Intercurrent Condition             0             0             0             0             0             0             0             0             0             0             1             0             0             1             0             0             1             1             0
Other Medical Condition             1             0             0             0             0             1             0             0             0             0             0             0             0             0             1             0             0             2             0
Physician Decision             0             0             0             0             0             1             0             0             0             2             0             0             0             1             2             1             2             2             0
[1]
Completed indicates participants continuing treatment as of 01 September 2017
Period Title: Safety Follow-up (Sept 2017 to July 2019
Started 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 16
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 14
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2
Reason Not Completed
Ongoing Treatment             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             0             2
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 30 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg BID Phase 1 Dose Escalation: Enasidenib 75 mg BID Phase 1 Dose Escalation: Enasidenib 100 mg BID Phase 1 Dose Escalation: Enasidenib 150 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg QD Phase 1 Dose Escalation: Enasidenib 75 mg QD Phase 1 Dose Escalation: Enasidenib 100 mg QD Phase 1 Dose Escalation: Enasidenib 150 mg QD Phase 1 Dose Escalation: Enasidenib 200 mg QD Phase 1 Dose Escalation: Enasidenib 300 mg QD Phase 1 Dose Escalation: Enasidenib 450 mg QD Phase 1 Dose Escalation: Enasidenib 650 mg QD Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD Phase 2: Enasidenib 100 mg QD Total
Hide Arm/Group Description Participants received enasidenib 30 mg tablets twice a day (BID) on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 50 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 75 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 150 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 50 mg tablets once a day (QD) on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 75 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 150 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 200 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 300 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 450 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 650 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants ≥ 60 years old with relapsed or refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants < 60 years old with relapsed, refractory AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Participants received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 7 7 7 8 5 9 7 22 6 14 9 5 7 49 25 25 27 106 345
Hide Baseline Analysis Population Description
The full analysis set includes all participants who received at least one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
62.6  (6.37) 61.3  (8.86) 64.7  (8.38) 67.6  (12.88) 73.6  (7.23) 71.8  (9.00) 62.3  (13.77) 63.9  (15.06) 73.8  (2.48) 67.5  (14.69) 68.3  (6.20) 70.0  (8.77) 70.1  (5.34) 70.5  (11.09) 49.2  (8.12) 76.4  (6.87) 68.1  (13.96) 66.5  (11.88) 66.8  (12.49)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
< 65 Years Old
3
  42.9%
5
  71.4%
3
  42.9%
2
  25.0%
1
  20.0%
2
  22.2%
2
  28.6%
10
  45.5%
0
   0.0%
6
  42.9%
2
  22.2%
1
  20.0%
1
  14.3%
11
  22.4%
25
 100.0%
1
   4.0%
4
  14.8%
35
  33.0%
114
  33.0%
≥ 65- < 75 Years Old
4
  57.1%
2
  28.6%
4
  57.1%
3
  37.5%
2
  40.0%
4
  44.4%
5
  71.4%
5
  22.7%
4
  66.7%
3
  21.4%
5
  55.6%
3
  60.0%
5
  71.4%
22
  44.9%
0
   0.0%
8
  32.0%
13
  48.1%
45
  42.5%
137
  39.7%
≥ 75 Years Old
0
   0.0%
0
   0.0%
0
   0.0%
3
  37.5%
2
  40.0%
3
  33.3%
0
   0.0%
7
  31.8%
2
  33.3%
5
  35.7%
2
  22.2%
1
  20.0%
1
  14.3%
16
  32.7%
0
   0.0%
16
  64.0%
10
  37.0%
26
  24.5%
94
  27.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
Female
3
  42.9%
5
  71.4%
4
  57.1%
4
  50.0%
4
  80.0%
4
  44.4%
0
   0.0%
11
  50.0%
3
  50.0%
3
  21.4%
1
  11.1%
1
  20.0%
1
  14.3%
27
  55.1%
12
  48.0%
9
  36.0%
10
  37.0%
42
  39.6%
144
  41.7%
Male
4
  57.1%
2
  28.6%
3
  42.9%
4
  50.0%
1
  20.0%
5
  55.6%
7
 100.0%
11
  50.0%
3
  50.0%
11
  78.6%
8
  88.9%
4
  80.0%
6
  85.7%
22
  44.9%
13
  52.0%
16
  64.0%
17
  63.0%
64
  60.4%
201
  58.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
1
  11.1%
1
  14.3%
2
   9.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
7
  14.3%
3
  12.0%
2
   8.0%
1
   3.7%
8
   7.5%
27
   7.8%
Not Hispanic or Latino
4
  57.1%
6
  85.7%
5
  71.4%
7
  87.5%
3
  60.0%
8
  88.9%
3
  42.9%
15
  68.2%
6
 100.0%
8
  57.1%
8
  88.9%
4
  80.0%
4
  57.1%
36
  73.5%
16
  64.0%
22
  88.0%
19
  70.4%
60
  56.6%
234
  67.8%
Unknown or Not Reported
3
  42.9%
1
  14.3%
1
  14.3%
1
  12.5%
2
  40.0%
0
   0.0%
3
  42.9%
5
  22.7%
0
   0.0%
6
  42.9%
1
  11.1%
1
  20.0%
2
  28.6%
6
  12.2%
6
  24.0%
1
   4.0%
7
  25.9%
38
  35.8%
84
  24.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
White
6
  85.7%
6
  85.7%
6
  85.7%
6
  75.0%
2
  40.0%
6
  66.7%
5
  71.4%
18
  81.8%
6
 100.0%
11
  78.6%
8
  88.9%
4
  80.0%
5
  71.4%
40
  81.6%
17
  68.0%
24
  96.0%
19
  70.4%
78
  73.6%
267
  77.4%
Black
1
  14.3%
1
  14.3%
0
   0.0%
1
  12.5%
0
   0.0%
2
  22.2%
1
  14.3%
0
   0.0%
0
   0.0%
1
   7.1%
0
   0.0%
0
   0.0%
1
  14.3%
1
   2.0%
4
  16.0%
0
   0.0%
0
   0.0%
6
   5.7%
19
   5.5%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.0%
0
   0.0%
0
   0.0%
2
   7.4%
0
   0.0%
4
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.9%
1
   0.3%
American Indian/Alaskan Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Other
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.0%
2
   8.0%
0
   0.0%
0
   0.0%
0
   0.0%
4
   1.2%
Not Provided
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
3
  60.0%
0
   0.0%
1
  14.3%
4
  18.2%
0
   0.0%
2
  14.3%
1
  11.1%
1
  20.0%
1
  14.3%
6
  12.2%
2
   8.0%
1
   4.0%
6
  22.2%
21
  19.8%
50
  14.5%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
0 - Fully active
1
  14.3%
1
  14.3%
2
  28.6%
4
  50.0%
2
  40.0%
0
   0.0%
2
  28.6%
7
  31.8%
1
  16.7%
2
  14.3%
2
  22.2%
3
  60.0%
1
  14.3%
10
  20.4%
5
  20.0%
6
  24.0%
6
  22.2%
24
  22.6%
79
  22.9%
1 - Restricted but ambulatory
4
  57.1%
6
  85.7%
5
  71.4%
4
  50.0%
2
  40.0%
5
  55.6%
4
  57.1%
11
  50.0%
4
  66.7%
9
  64.3%
4
  44.4%
1
  20.0%
5
  71.4%
28
  57.1%
18
  72.0%
13
  52.0%
16
  59.3%
65
  61.3%
204
  59.1%
2 - Ambulatory but unable to work
2
  28.6%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
4
  44.4%
1
  14.3%
4
  18.2%
1
  16.7%
3
  21.4%
3
  33.3%
1
  20.0%
1
  14.3%
11
  22.4%
2
   8.0%
6
  24.0%
5
  18.5%
16
  15.1%
61
  17.7%
3 - Limited self-care
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4 - Completely Disabled
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.9%
1
   0.3%
[1]
Measure Description: ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: -0 = Fully active, no restrictions; -1 = Restricted activity but ambulatory, able to carry out work of a light nature; -2 = Ambulatory and capable of all self-care but unable to carry out work activities; -3 = Limited self-care, confined to bed or chair more than 50% of waking hours; -4 = Completely disabled, no self-care, confined to bed or chair; -5 = Dead
Isocitrate dehydrogenase 2 (IDH2) Mutation Type   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
R140
6
  85.7%
6
  85.7%
6
  85.7%
5
  62.5%
2
  40.0%
6
  66.7%
6
  85.7%
19
  86.4%
5
  83.3%
10
  71.4%
9
 100.0%
1
  20.0%
5
  71.4%
37
  75.5%
18
  72.0%
17
  68.0%
21
  77.8%
80
  75.5%
259
  75.1%
R172
1
  14.3%
1
  14.3%
1
  14.3%
3
  37.5%
2
  40.0%
3
  33.3%
1
  14.3%
3
  13.6%
1
  16.7%
4
  28.6%
0
   0.0%
4
  80.0%
2
  28.6%
12
  24.5%
7
  28.0%
8
  32.0%
5
  18.5%
26
  24.5%
84
  24.3%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.7%
0
   0.0%
2
   0.6%
[1]
Measure Description: Isocitrate dehydrogenase 2 (IDH2) gene mutations have been described in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Mutations in IDH2 most commonly lead to alterations affecting arginine-172 (R172) or arginine-140 (R140) in IDH2.
Uridine Diphosphate-Glucuronosyltransferase 1 Family, Polypeptide A1 (UGT1A1) Mutation Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
Heterozygous
0
   0.0%
0
   0.0%
0
   0.0%
1
  12.5%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.5%
2
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.0%
0
   0.0%
1
   4.0%
1
   3.7%
20
  18.9%
27
   7.8%
Homozygous
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
  14.3%
1
   2.0%
0
   0.0%
2
   8.0%
1
   3.7%
10
   9.4%
16
   4.6%
Wild Type
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
1
   3.7%
20
  18.9%
22
   6.4%
Not Applicable
7
 100.0%
7
 100.0%
7
 100.0%
7
  87.5%
5
 100.0%
9
 100.0%
7
 100.0%
21
  95.5%
4
  66.7%
14
 100.0%
8
  88.9%
5
 100.0%
6
  85.7%
47
  95.9%
24
  96.0%
21
  84.0%
23
  85.2%
36
  34.0%
258
  74.8%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
0
   0.0%
1
   3.7%
20
  18.9%
22
   6.4%
[1]
Measure Description:

The UGT1A1 gene produces a protein, called the bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme, an enzyme that glucuronidates bilirubin, a substance produced when red blood cells are broken down. This enzyme converts the toxic form of bilirubin (unconjugated bilirubin) to its nontoxic form (conjugated bilirubin), making it able to be dissolved and removed from the body. Enasidenib is an inhibitor of UGT1A1.

Screening for UGT1A1 mutation was added in Protocol Amendment 4 therefore data are not not available for participants enrolled prior to Amendment 4.

Cytogenetic Risk Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
Favorable-Risk
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Intermediate-Risk
4
  57.1%
5
  71.4%
1
  14.3%
2
  25.0%
1
  20.0%
5
  55.6%
2
  28.6%
6
  27.3%
4
  66.7%
9
  64.3%
6
  66.7%
3
  60.0%
3
  42.9%
19
  38.8%
14
  56.0%
13
  52.0%
19
  70.4%
57
  53.8%
173
  50.1%
Poor-Risk
1
  14.3%
1
  14.3%
2
  28.6%
2
  25.0%
2
  40.0%
3
  33.3%
1
  14.3%
8
  36.4%
1
  16.7%
2
  14.3%
0
   0.0%
1
  20.0%
3
  42.9%
13
  26.5%
8
  32.0%
8
  32.0%
2
   7.4%
26
  24.5%
84
  24.3%
Failure
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   4.1%
0
   0.0%
0
   0.0%
0
   0.0%
6
   5.7%
9
   2.6%
Missing
2
  28.6%
1
  14.3%
3
  42.9%
4
  50.0%
2
  40.0%
1
  11.1%
4
  57.1%
8
  36.4%
1
  16.7%
3
  21.4%
3
  33.3%
1
  20.0%
1
  14.3%
15
  30.6%
3
  12.0%
4
  16.0%
6
  22.2%
17
  16.0%
79
  22.9%
[1]
Measure Description: Cytogenetic risk classification according to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Acute Myeloid Leukemia. Risk categories are based on analysis of cytogenetics (the study of chromosomes), including chromosomal deletions, duplications, or substitutions and analysis of molecular abnormalities such as specific mutations. Better risk indicates disease more likely to respond to initial treatment and less likely to relapse whereas poor-risk is characterized by poor response to induction chemotherapy and higher relapse rates.
Bone Marrow Blasts  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
< 20% Blasts
1
  14.3%
4
  57.1%
1
  14.3%
3
  37.5%
1
  20.0%
0
   0.0%
2
  28.6%
6
  27.3%
2
  33.3%
4
  28.6%
3
  33.3%
0
   0.0%
2
  28.6%
11
  22.4%
6
  24.0%
2
   8.0%
16
  59.3%
22
  20.8%
86
  24.9%
20% to < 30% Blasts
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  20.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
  16.7%
1
   7.1%
1
  11.1%
0
   0.0%
0
   0.0%
4
   8.2%
2
   8.0%
6
  24.0%
2
   7.4%
14
  13.2%
34
   9.9%
30% to < 50% Blasts
5
  71.4%
2
  28.6%
1
  14.3%
2
  25.0%
1
  20.0%
2
  22.2%
0
   0.0%
5
  22.7%
2
  33.3%
5
  35.7%
2
  22.2%
2
  40.0%
1
  14.3%
8
  16.3%
4
  16.0%
6
  24.0%
3
  11.1%
18
  17.0%
69
  20.0%
≥ 50% Blasts
1
  14.3%
1
  14.3%
4
  57.1%
3
  37.5%
2
  40.0%
6
  66.7%
4
  57.1%
11
  50.0%
1
  16.7%
4
  28.6%
3
  33.3%
3
  60.0%
4
  57.1%
26
  53.1%
12
  48.0%
10
  40.0%
6
  22.2%
49
  46.2%
150
  43.5%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.0%
1
   4.0%
0
   0.0%
3
   2.8%
6
   1.7%
Malignancy Type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 106 participants 345 participants
Relapsed / Refractory Acute Myeloid Leukemia (AML)
6
  85.7%
7
 100.0%
6
  85.7%
6
  75.0%
3
  60.0%
8
  88.9%
5
  71.4%
19
  86.4%
3
  50.0%
9
  64.3%
8
  88.9%
3
  60.0%
7
 100.0%
48
  98.0%
25
 100.0%
3
  12.0%
9
  33.3%
105
  99.1%
280
  81.2%
Untreated AML
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
2
  40.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
  16.7%
3
  21.4%
0
   0.0%
2
  40.0%
0
   0.0%
1
   2.0%
0
   0.0%
22
  88.0%
5
  18.5%
1
   0.9%
39
  11.3%
Myelodysplastic Syndrome (MDS)
1
  14.3%
0
   0.0%
0
   0.0%
2
  25.0%
0
   0.0%
0
   0.0%
1
  14.3%
3
  13.6%
1
  16.7%
1
   7.1%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7
  25.9%
0
   0.0%
17
   4.9%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
  16.7%
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6
  22.2%
0
   0.0%
9
   2.6%
Hemoglobin   [1] 
Median (Full Range)
Unit of measure:  g/L
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 105 participants 344 participants
82.0
(72.0 to 95.0)
97.0
(82.0 to 138.0)
86.0
(76.0 to 111.0)
97.5
(75.0 to 109.0)
91.0
(75.0 to 93.0)
89.0
(77.0 to 102.0)
92.0
(73.0 to 110.0)
96.5
(78.0 to 124.0)
94.0
(79.0 to 132.0)
87.5
(76.0 to 125.0)
93.0
(78.0 to 131.0)
103.0
(70.0 to 121.0)
95.0
(76.0 to 122.0)
93.0
(69.0 to 125.0)
93.0
(70.0 to 129.0)
89.0
(70.0 to 111.0)
92.0
(71.0 to 152.0)
89.0
(70.0 to 156.0)
90.0
(69.0 to 156.0)
[1]
Measure Analysis Population Description: Participants with available data.
Platelets   [1] 
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 105 participants 344 participants
43.0
(15.0 to 147.0)
91.0
(13.0 to 158.0)
102.0
(17.0 to 167.0)
92.0
(14.0 to 507.0)
44.0
(26.0 to 183.0)
23.0
(12.0 to 287.0)
52.0
(8.0 to 253.0)
35.5
(5.0 to 194.0)
48.0
(12.0 to 72.0)
42.0
(9.0 to 282.0)
63.0
(21.0 to 486.0)
73.0
(29.0 to 170.0)
45.9
(17.0 to 247.0)
39.0
(1.0 to 197.0)
37.0
(6.0 to 292.0)
58.0
(12.0 to 529.0)
57.0
(13.0 to 644.0)
36.0
(2.0 to 1288.0)
42.9
(1.0 to 1228.0)
[1]
Measure Analysis Population Description: Participants with available data
Absolute Neutrophil Count (ANC)   [1] 
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 7 participants 6 participants 6 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 12 participants 9 participants 5 participants 7 participants 49 participants 25 participants 23 participants 27 participants 105 participants 338 participants
0.8
(0.0 to 12.6)
1.1
(0.4 to 4.7)
0.5
(0.0 to 15.5)
0.3
(0.0 to 2.0)
0.5
(0.0 to 2.1)
0.2
(0.0 to 3.4)
0.2
(0.0 to 1.4)
0.5
(0.0 to 32.1)
1.0
(0.1 to 2.5)
0.4
(0.1 to 7.4)
0.6
(0.1 to 11.0)
0.1
(0.1 to 1.1)
0.8
(0.1 to 3.4)
0.4
(0.0 to 5.4)
0.1
(0.0 to 4.4)
0.4
(0.0 to 6.7)
1.0
(0.1 to 11.7)
0.3
(0.0 to 70.0)
0.4
(0.0 to 70.0)
[1]
Measure Analysis Population Description: Participants with available data
White Blood Cell Count   [1] 
Median (Full Range)
Unit of measure:  10^9 cells/L
Number Analyzed 7 participants 7 participants 7 participants 8 participants 5 participants 9 participants 7 participants 22 participants 6 participants 14 participants 9 participants 5 participants 7 participants 49 participants 25 participants 25 participants 27 participants 105 participants 344 participants
2.0
(0.6 to 57.2)
2.1
(0.3 to 31.3)
2.0
(0.2 to 39.7)
2.5
(0.4 to 12.1)
1.9
(1.5 to 16.8)
2.6
(0.5 to 20.2)
2.1
(0.5 to 14.7)
5.3
(0.6 to 88.2)
3.3
(0.8 to 26.9)
2.6
(0.5 to 34.5)
2.4
(0.7 to 47.9)
1.3
(0.7 to 17.0)
3.6
(0.8 to 38.3)
3.0
(0.2 to 64.5)
3.1
(0.4 to 26.9)
2.3
(0.3 to 25.7)
2.7
(0.4 to 26.7)
2.0
(0.2 to 93.8)
2.4
(0.2 to 93.8)
[1]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Phase 1 Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLT)
Hide Description

Toxicity severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT was defined as:

  • Non-hematologic toxicities: CTCAE ≥ Grade 3 with the exception of ≥ Grade 3 blood bilirubin increases in participants with a uridine diphosphate- glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) mutation. In participants with a UGT1A1 mutation, blood bilirubin increases of > 5× upper limit of normal (ULN) were considered a DLT.
  • Hematologic toxicities: Prolonged myelosuppression, defined as persistence of ≥ Grade 3 neutropenia or thrombocytopenia (by NCI CTCAE v4.03), leukemia-specific criteria, i.e., marrow cellularity <5% on Day 28 or later from the start of study drug without evidence of leukemia) at least 42 days after the initiation of Cycle 1 therapy. Leukemia-specific grading was used for cytopenias (based on percentage decrease from Baseline: 50 to 75% = Grade 3, >75% = Grade 4)
Time Frame From time of first dose up to the end of Cycle 1; 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who took at least one dose of study drug in the dose escalation phase and either had a DLT during Cycle 1, regardless of the amount of study drug exposure, or had no DLT and completed at least 75% of their planned Cycle 1 doses, and were considered to have had enough safety data to conclude that a DLT did not occur during Cycle 1.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 30 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg BID Phase 1 Dose Escalation: Enasidenib 75 mg BID Phase 1 Dose Escalation: Enasidenib 100 mg BID Phase 1 Dose Escalation: Enasidenib 150 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg QD Phase 1 Dose Escalation: Enasidenib 75 mg QD Phase 1 Dose Escalation: Enasidenib 100 mg QD Phase 1 Dose Escalation: Enasidenib 150 mg QD Phase 1 Dose Escalation: Enasidenib 200 mg QD Phase 1 Dose Escalation: Enasidenib 300 mg QD Phase 1 Dose Escalation: Enasidenib 450 mg QD Phase 1 Dose Escalation: Enasidenib 650 mg QD
Hide Arm/Group Description:
Participants received enasidenib 30 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 50 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 75 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 100 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 150 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 50 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 75 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 100 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 150 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 200 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 300 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 450 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 650 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 4 5 5 7 4 0 0 5 6 6 4 5 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0 0
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
2.Primary Outcome
Title Phase 1 Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria:

  • Resulted in death;
  • Was life threatening;
  • Requires inpatient hospitalization or prolongation of existing hospitalization;
  • Resulted in persistent or significant disability/incapacity;
  • Was a congenital anomaly/birth defect;
  • Was medically important.

The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time Frame From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff date of 01 September 2017; median treatment duration in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set includes all participants who received at least 1 dose of study treatment.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 30 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg BID Phase 1 Dose Escalation: Enasidenib 75 mg BID Phase 1 Dose Escalation: Enasidenib 100 mg BID Phase 1 Dose Escalation: Enasidenib 150 mg BID Phase 1 Dose Escalation: Enasidenib 50 mg QD Phase 1 Dose Escalation: Enasidenib 75 mg QD Phase 1 Dose Escalation: Enasidenib 100 mg QD Phase 1 Dose Escalation: Enasidenib 150 mg QD Phase 1 Dose Escalation: Enasidenib 200 mg QD Phase 1 Dose Escalation: Enasidenib 300 mg QD Phase 1 Dose Escalation: Enasidenib 450 mg QD Phase 1 Dose Escalation: Enasidenib 650 mg QD
Hide Arm/Group Description:
Participants received enasidenib 30 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 50 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 75 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 100 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 150 mg tablets BID on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 50 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 75 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 100 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 150 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 200 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 300 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 450 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants received enasidenib 650 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 7 7 7 8 5 9 7 22 6 14 9 5 7
Measure Type: Count of Participants
Unit of Measure: Participants
Any treatment-emergent adverse event (TEAE)
7
 100.0%
7
 100.0%
7
 100.0%
8
 100.0%
5
 100.0%
9
 100.0%
7
 100.0%
22
 100.0%
6
 100.0%
14
 100.0%
9
 100.0%
5
 100.0%
7
 100.0%
TEAE Related to Investigational Product (IP)
6
  85.7%
7
 100.0%
6
  85.7%
5
  62.5%
5
 100.0%
3
  33.3%
3
  42.9%
17
  77.3%
6
 100.0%
14
 100.0%
7
  77.8%
4
  80.0%
7
 100.0%
Grade 3-4 TEAE
7
 100.0%
5
  71.4%
6
  85.7%
8
 100.0%
4
  80.0%
9
 100.0%
6
  85.7%
21
  95.5%
5
  83.3%
14
 100.0%
8
  88.9%
5
 100.0%
7
 100.0%
Grade 3-4 TEAE Related to IP
4
  57.1%
2
  28.6%
3
  42.9%
3
  37.5%
1
  20.0%
3
  33.3%
1
  14.3%
10
  45.5%
3
  50.0%
9
  64.3%
5
  55.6%
4
  80.0%
4
  57.1%
Grade 5 TEAE
4
  57.1%
1
  14.3%
2
  28.6%
2
  25.0%
2
  40.0%
3
  33.3%
1
  14.3%
5
  22.7%
0
   0.0%
2
  14.3%
4
  44.4%
2
  40.0%
0
   0.0%
Grade 5 TEAE Related to IP
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Serious TEAE
6
  85.7%
6
  85.7%
6
  85.7%
7
  87.5%
3
  60.0%
9
 100.0%
5
  71.4%
19
  86.4%
4
  66.7%
11
  78.6%
7
  77.8%
5
 100.0%
6
  85.7%
Serious TEAE Related to IP
2
  28.6%
4
  57.1%
2
  28.6%
2
  25.0%
0
   0.0%
2
  22.2%
1
  14.3%
9
  40.9%
1
  16.7%
5
  35.7%
3
  33.3%
2
  40.0%
2
  28.6%
TEAE Leading to Discontinuation (D/C) of IP
3
  42.9%
0
   0.0%
1
  14.3%
1
  12.5%
0
   0.0%
0
   0.0%
1
  14.3%
5
  22.7%
1
  16.7%
4
  28.6%
3
  33.3%
2
  40.0%
2
  28.6%
TEAE Related to IP Leading to D/C of IP
1
  14.3%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
0
   0.0%
1
   7.1%
0
   0.0%
1
  20.0%
1
  14.3%
TEAE Leading to Reduction of IP
0
   0.0%
1
  14.3%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
2
  33.3%
3
  21.4%
1
  11.1%
3
  60.0%
6
  85.7%
TEAE Related to IP Leading to Reduction of IP
0
   0.0%
1
  14.3%
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   9.1%
0
   0.0%
2
  14.3%
1
  11.1%
3
  60.0%
6
  85.7%
TEAE Leading to Interruption of IP
4
  57.1%
1
  14.3%
3
  42.9%
5
  62.5%
2
  40.0%
6
  66.7%
0
   0.0%
10
  45.5%
2
  33.3%
9
  64.3%
3
  33.3%
3
  60.0%
6
  85.7%
TEAE Related to IP Leading to Interruption of IP
2
  28.6%
0
   0.0%
2
  28.6%
3
  37.5%
1
  20.0%
1
  11.1%
0
   0.0%
7
  31.8%
2
  33.3%
7
  50.0%
2
  22.2%
2
  40.0%
6
  85.7%
3.Primary Outcome
Title Phase 1 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events
Hide Description

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria:

  • Resulted in death;
  • Was life threatening;
  • Required inpatient hospitalization or prolongation of existing hospitalization;
  • Resulted in persistent or significant disability/incapacity;
  • Was a congenital anomaly/birth defect;
  • Was medically important.

The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time Frame From the first dose of investigational product (IP) up to 28 days after the last dose of IP up to the data cutoff date of 01 September 2017; median treatment duration in Part 1 Expansion was 5.2 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Phase 1 Expansion who received at least 1 dose of study treatment.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed or refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with relapsed, refractory AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 49 25 25 27
Measure Type: Count of Participants
Unit of Measure: Participants
Any Treatment-emergent Adverse Event (TEAE) 49 24 25 27
TEAE Related to Investigational Product (IP) 43 18 22 23
Grade 3-4 TEAE 47 21 21 20
Grade 3-4 TEAE Related to IP 20 9 15 7
Grade 5 TEAE 8 2 8 6
Grade 5 TEAE Related to IP 0 0 1 0
Serious TEAE 41 19 20 17
Serious TEAE Related to IP 7 6 8 2
TEAE Leading to Discontinuation (D/C) of IP 6 2 8 4
TEAE Related to IP Leading to D/C of IP 2 0 2 1
TEAE Leading to Reduction of IP 1 0 0 3
TEAE Related to IP Leading to Reduction of IP 0 0 0 3
TEAE Leading to IP Interruption 24 10 16 9
TEAE Related to IP Leading to Interruption of IP 9 3 7 3
4.Primary Outcome
Title Phase 2 Dose Expansion: Investigator Assessed Overall Response Rate (ORR)
Hide Description

ORR is defined as the percentage of participants achieving an overall response of complete response (CR), CR with incomplete neutrophil recovery (CRi), CR with incomplete platelet recovery (CRp), partial response (PR), or morphologic leukemia-free state (MLFS) based on the 2003 revised International Working Group (IWG) criteria for AML, assessed by the Investigator.

CR:

  • Absolute neutrophil count (ANC) > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelets < 100 x 10⁹/L)

PR:

  • Meets hematologic criteria of CR
  • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.

MLFS:

  • Bone marrow blasts < 5%
  • Absence of blasts with Auer rods
  • Absence of extramedullary disease
  • No hematologic recovery required
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37.1
(27.9 to 47.1)
5.Primary Outcome
Title Phase 2 Dose Expansion: Number of Participants With Treatment Emergent Adverse Events
Hide Description

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria:

  • Resulted in death;
  • Was life threatening;
  • Required inpatient hospitalization or prolongation of existing hospitalization;
  • Resulted in persistent or significant disability/incapacity;
  • Was a congenital anomaly/birth defect;
  • Was medically important.

The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time Frame From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff of date of 01 September 2017; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Count of Participants
Unit of Measure: Participants
Any Treatment-emergent Adverse Event (TEAE) 105
TEAE Related to Investigational Product (IP) 88
Grade 3-4 TEAE 92
Grade 3-4 TEAE Related to IP 48
Grade 5 TEAE 30
Grade 5 TEAE Related to IP 1
Serious TEAE 85
Serious TEAE Related to IP 34
TEAE Leading to Discontinuation (D/C) of IP 22
TEAE Related to IP Leading to D/C of IP 5
TEAE Leading to Reduction of IP 9
TEAE Related to IP Leading to Reduction of IP 7
TEAE Leading to Interruption of IP 49
TEAE Related to IP Leading to Interruption of IP 23
6.Primary Outcome
Title Safety Follow-up: Number of Participants With Treatment Emergent Adverse Events
Hide Description

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria:

  • Resulted in death;
  • Was life threatening;
  • Required inpatient hospitalization or prolongation of existing hospitalization;
  • Resulted in persistent or significant disability/incapacity;
  • Was a congenital anomaly/birth defect;
  • Was medically important.

The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time Frame From the primary analysis cut-off date of 01 September 2017 to the final analysis cut-off date of 29 July 2019, a maximum of 23 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study treatment during the Safety Follow-up Period.
Arm/Group Title Safety Follow-up: Enasidenib
Hide Arm/Group Description:
Participants remaining on treatment as of the 01 September 2017 data cut-off date continued to receive enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 16
Measure Type: Count of Participants
Unit of Measure: Participants
Any treatment-emergent adverse event (TEAE)
16
 100.0%
TEAE Related to Investigational Product (IP)
6
  37.5%
Grade 3-4 TEAE
13
  81.3%
Grade 3-4 TEAE Related to IP
3
  18.8%
Grade 5 TEAE
0
   0.0%
Grade 5 TEAE Related to IP
0
   0.0%
Serious TEAE
9
  56.3%
Serious TEAE Related to IP
1
   6.3%
TEAE Leading to Discontinuation (D/C) of IP
0
   0.0%
TEAE Related to IP Leading to D/C of IP
0
   0.0%
TEAE Leading to Reduction of IP
0
   0.0%
TEAE Related to IP Leading to Reduction of IP
0
   0.0%
TEAE Leading to Interruption of IP
4
  25.0%
TEAE Related to IP Leading to Interruption of IP
0
   0.0%
7.Secondary Outcome
Title Phase 1 Dose Escalation: Investigator Assessed Overall Response Rate (ORR) by Total Daily Dose
Hide Description

ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, marrow CR (mCR) (for MDS) and MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)

PR:

  • Meets hematologic criteria of CR
  • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.

MLFS:

  • Bone marrow blasts < 5%
  • Absence of blasts with Auer rods
  • Absence of extramedullary disease
  • No hematologic recovery required

mCR:

  • Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 50 mg Phase 1 Dose Escalation: Enasidenib 60 mg Phase 1 Dose Escalation: Enasidenib 75 mg Phase 1 Dose Escalation: Enasidenib 100 mg Phase 1 Dose Escalation: Enasidenib 150 mg Phase 1 Dose Escalation: Enasidenib 200 mg Phase 1 Dose Escalation: Enasidenib 300 mg Phase 1 Dose Escalation: Enasidenib 450 mg Phase 1 Dose Escalation: Enasidenib 650 mg
Hide Arm/Group Description:
Participants received enasidenib 50 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 60 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 75 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 100 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 150 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 200 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 300 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 450 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 650 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 9 7 7 29 13 22 14 5 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(7.5 to 70.1)
42.9
(9.9 to 81.6)
14.3
(0.4 to 57.9)
44.8
(26.4 to 64.3)
46.2
(19.2 to 74.9)
50.0
(28.2 to 71.8)
35.7
(12.8 to 64.9)
60.0
(14.7 to 94.7)
71.4
(29.0 to 96.3)
8.Secondary Outcome
Title Phase 1 Dose Expansion: Investigator Assessed Overall Response Rate (ORR)
Hide Description

ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, mCR (for MDS), or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)

PR:

  • Meets hematologic criteria of CR
  • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.

MLFS:

  • Bone marrow blasts < 5%
  • Absence of blasts with Auer rods
  • Absence of extramedullary disease
  • No hematologic recovery required

mCR:

  • Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment in Phase 1 Expansion.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed, refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 49 25 25 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.9
(32.5 to 61.7)
20.0
(6.8 to 40.7)
36.0
(18.0 to 57.5)
44.4
(25.5 to 64.7)
9.Secondary Outcome
Title Combined Phase 1/2: Investigator Assessed Overall Response Rate in Participants With R/R AML
Hide Description

For participants with R/R AML ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)

PR:

  • Meets hematologic criteria of CR
  • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.

MLFS:

  • Bone marrow blasts < 5%
  • Absence of blasts with Auer rods
  • Absence of extramedullary disease
  • No hematologic recovery required
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure for Phase 1 and 2 R/R AML participants was 5.4 months (range 0.4 to 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Phase 1 and 2 with R/R AML who received at least one dose of study treatment.
Arm/Group Title Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants in Phase 1 or 2 with relapsed or refractory (R/R) AML who received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 214
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
38.8
(32.2 to 45.7)
10.Secondary Outcome
Title Phase 1 Dose Escalation: Complete Response Rate (CRR) by Total Daily Dose
Hide Description

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator.

CR for AML:

  • Absolute neutrophil count (ANC) > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CR for MDS:

  • Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines
  • Peripheral blood:

    • Hemoglobin ≥ 11 g/dL
    • Platelets ≥ 100 × 10⁹/L
    • Neutrophils ≥ 1.0 × 10⁹/L
    • Blasts = 0%
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 50 mg Phase 1 Dose Escalation: Enasidenib 60 mg Phase 1 Dose Escalation: Enasidenib 75 mg Phase 1 Dose Escalation: Enasidenib 100 mg Phase 1 Dose Escalation: Enasidenib 150 mg Phase 1 Dose Escalation: Enasidenib 200 mg Phase 1 Dose Escalation: Enasidenib 300 mg Phase 1 Dose Escalation: Enasidenib 450 mg Phase 1 Dose Escalation: Enasidenib 650 mg
Hide Arm/Group Description:
Participants received enasidenib 50 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 60 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 75 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 100 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 150 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 200 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 300 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 450 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 650 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 9 7 7 29 13 22 14 5 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.2
(2.8 to 60.0)
14.3
(0.4 to 57.9)
0.0
(0.0 to 41.0)
27.6
(12.7 to 47.2)
15.4
(1.9 to 45.4)
4.5
(0.1 to 22.8)
21.4
(4.7 to 50.8)
40.0
(5.3 to 85.3)
28.6
(3.7 to 71.0)
11.Secondary Outcome
Title Phase 1 Dose Expansion: Complete Response Rate
Hide Description

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator.

CR for AML:

  • Absolute neutrophil count (ANC) > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CR for MDS:

  • Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines
  • Peripheral blood:

    • Hemoglobin ≥ 11 g/dL
    • Platelets ≥ 100 × 10⁹/L
    • Neutrophils ≥ 1.0 × 10⁹/L
    • Blasts = 0%
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed, refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 49 25 25 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.4
(11.8 to 36.6)
0.0
(0.0 to 13.7)
20.0
(6.8 to 40.7)
22.2
(8.6 to 42.3)
12.Secondary Outcome
Title Phase 2 Dose Expansion: Complete Response Rate
Hide Description

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML as assessed by the investigator.

CR for AML:

  • Absolute neutrophil count (ANC) > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.0
(12.8 to 28.9)
13.Secondary Outcome
Title Phase 1 Dose Escalation: Rate of Complete Response and Complete Response With Incomplete Hematological Recovery (CR/CRi/CRp) by Total Daily Dose
Hide Description

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp), based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator review.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.
Arm/Group Title Phase 1 Dose Escalation: Enasidenib 50 mg Phase 1 Dose Escalation: Enasidenib 60 mg Phase 1 Dose Escalation: Enasidenib 75 mg Phase 1 Dose Escalation: Enasidenib 100 mg Phase 1 Dose Escalation: Enasidenib 150 mg Phase 1 Dose Escalation: Enasidenib 200 mg Phase 1 Dose Escalation: Enasidenib 300 mg Phase 1 Dose Escalation: Enasidenib 450 mg Phase 1 Dose Escalation: Enasidenib 650 mg
Hide Arm/Group Description:
Participants received enasidenib 50 mg tablets QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 60 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 75 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 100 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 150 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 200 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 300 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 450 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants who received a total daily dose of enasidenib 650 mg on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 9 7 7 29 13 22 14 5 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.2
(2.8 to 60.0)
14.3
(0.4 to 57.9)
0.0
(0.0 to 41.0)
31.0
(15.3 to 50.8)
15.4
(1.9 to 45.4)
18.2
(5.2 to 40.3)
28.6
(8.4 to 58.1)
40.0
(5.3 to 85.3)
57.1
(18.4 to 90.1)
14.Secondary Outcome
Title Phase 1 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp)
Hide Description

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the investigator.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study treatment in Phase 1 Dose Expansion.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed, refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 49 25 25 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.6
(16.6 to 43.3)
8.0
(1.0 to 26.0)
24.0
(9.4 to 45.1)
25.9
(11.1 to 46.3)
15.Secondary Outcome
Title Phase 2 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp)
Hide Description

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML, assessed by the Investigator.

CR:

  • ANC > 1.0 x10⁹/L
  • Platelet count > 100 x10⁹/L
  • Bone marrow (BM) blasts < 5%
  • Absence of blasts with Auer rods
  • Independence of red cell transfusions

CRi:

  • All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L

CRp:

  • All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
Time Frame Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
31.4
(22.7 to 41.2)
16.Secondary Outcome
Title Phase 1 Dose Expansion: Kaplan-Meier Estimate of Duration of Response (DOR)
Hide Description

Among participants who had a response of CR, CRi, CRp, PR, mCR, or MLFS based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method.

Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.

Time Frame From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study treatment in Phase 1 Dose Expansion with an objective response.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed, refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 23 5 9 12
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(1.9 to 18.5)
3.9
(1.9 to 5.1)
NA [1] 
(1.9 to NA)
12.0 [1] 
(0.4 to NA)
[1]
Not estimable due to low number of events
17.Secondary Outcome
Title Phase 2 Dose Expansion: Kaplan-Meier Estimate of Duration of Response
Hide Description

For participants with an objective response based on the 2003 revised IWG criteria for AML assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. Participants without relapse, progressive disease or death were censored at the last response assessment date.

Relapse (for participants who previously attained CR, Cri, CRp or MLFS): BM blasts ≥ 5%, reappearance of blasts in the blood or development of extramedullary disease.

Disease progression (for participants who previously attained PR): development of new extramedullary disease, or

For participants with 5% to 67% BM blasts at nadir:

  • a > 50% increase in BM blasts from nadir and that is ≥ 20%.

For participants with ≥ 67% BM blasts at nadir:

  • a doubling of the nadir absolute peripheral blood (PB) blast count and the final absolute PB blast count > 10 x 10⁹/L.
Time Frame From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had an objective response.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 39
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(3.7 to 7.4)
18.Secondary Outcome
Title Phase 1 Dose Expansion: Kaplan-Meier Estimate of Overall Survival
Hide Description Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.
Time Frame From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants ≥ 60 years old with relapsed, refractory AML or participants of any age if relapsed post-bone marrow transplant (BMT) received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants < 60 years old with R/R AML, excluding participants who relapsed post-BMT, received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Untreated AML participants ≥ 60 years old who declined standard of care received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants with advanced hematologic malignancies not eligible for Arms 1 to 3 received 100 mg enasidenib QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 49 25 25 27
Median (95% Confidence Interval)
Unit of Measure: months
8.8
(7.5 to 10.5)
11.6
(6.5 to 15.4)
10.6
(6.2 to 19.8)
11.3
(3.6 to 19.1)
19.Secondary Outcome
Title Phase 2 Dose Expansion: Kaplan-Meier Estimate of Overall Survival
Hide Description Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.
Time Frame From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Median (95% Confidence Interval)
Unit of Measure: months
7.0
(4.9 to 8.8)
20.Secondary Outcome
Title Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline
Hide Description

Participants who achieved 56-day post-baseline red blood cell (RBC) transfusion independence, i.e. with no RBC transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline RBC transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 28 days before and 28 days after the first dose of treatment for Phase 1.

Results are reported for all participants in Phase 1 combined and for the subset of participants with R/R AML.

Time Frame Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The population included all participants who received at least one dose of study treatment in Phase 1 Dose Escalation and Dose Expansion. Results were analyzed and are reported for Phase 1 combined.
Arm/Group Title Phase 1: Enasidenib - R/R AML Phase 1: Enasidenib
Hide Arm/Group Description:
Participants in Phase 1 Dose Escalation and Phase 1 Dose Expansion with R/R AML who received any dose of enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants in Phase 1 Dose Escalation and Phase 1 Dose Expansion who received any dose of enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 175 239
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Transfusion Dependent Number Analyzed 135 participants 182 participants
39.3 38.5
Baseline Transfusion Independent Number Analyzed 40 participants 57 participants
80.0 71.9
21.Secondary Outcome
Title Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline
Hide Description

Participants who achieved 56-day post-baseline platelet transfusion independence, i.e. with no platelet transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline platelet transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 28 days before and 28 days after the first dose of treatment for Phase 1.

Results are reported for all participants in Phase 1 combined and for the subset of participants with R/R AML.

Time Frame Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).
Hide Outcome Measure Data
Hide Analysis Population Description
The population included all participants who received at least one dose of study treatment in Phase 1 Dose Escalation and Dose Expansion. Results were analyzed and are reported for Phase 1 combined.
Arm/Group Title Phase 1: Enasidenib - R/R AML Phase 1: Enasidenib
Hide Arm/Group Description:
Participants in Phase 1 Dose Escalation and Phase 1 Dose Expansion with R/R AML who received any dose of enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Participants in Phase 1 Dose Escalation and Phase 1 Dose Expansion who received any dose of enasidenib on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 175 239
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Transfusion Dependent Number Analyzed 106 participants 136 participants
38.7 33.1
Baseline Transfusion Independent Number Analyzed 69 participants 103 participants
78.3 76.7
22.Secondary Outcome
Title Phase 2: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline
Hide Description Participants who achieved 56-day post-baseline red blood cell (RBC) transfusion independence, i.e. with no RBC transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline RBC transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.
Time Frame Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Transfusion Dependent Number Analyzed 67 participants
41.8
Baseline Transfusion Independent Number Analyzed 38 participants
57.9
23.Secondary Outcome
Title Phase 2: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline
Hide Description Participants who achieved 56-day post-baseline platelet transfusion independence, i.e. with no platelet transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline platelet transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.
Time Frame Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.
Arm/Group Title Phase 2: Enasidenib 100 mg QD
Hide Arm/Group Description:
Participants with relapsed or refractory (R/R) AML received enasidenib 100 mg QD on Day 1 to Day 28 of each 28-day treatment cycle until disease progression or development of unacceptable toxicity.
Overall Number of Participants Analyzed 105
Measure Type: Number
Unit of Measure: percentage of participants
Baseline Transfusion Dependent Number Analyzed 59 participants
35.6
Baseline Transfusion Independent Number Analyzed 46 participants
69.6
24.Secondary Outcome
Title Phase 1 Dose Expansion: Kaplan-Meier Estimate of Event Free Survival (EFS)
Hide Description Event-free survival is defined as the interval from the date of the first dose to the date of documented relapse, progression, or death due to any cause, whichever occurs first. Participants without an EFS event were censored at the date of the last adequate response assessment.
Time Frame From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.
Arm/Group Title Phase 1 Dose Expansion Arm 1: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 2: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 3: Enasidenib 100 mg QD Phase 1 Dose Expansion Arm 4: Enasidenib 100 mg QD