Trial Outcomes & Findings for Study of Orally Administered Enasidenib (AG-221) in Adults With Advanced Solid Tumors, Including Glioma, or Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation (NCT NCT02273739)

NCT ID: NCT02273739

Last Updated: 2021-02-23

Results Overview

Treatment-emergent adverse events included any adverse events (AEs) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of the study drug. Severity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 or according to the following scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Fatal, death related to AE. A serious AE is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required or prolonged existing inpatient hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. Relationship to study drug administration was determined by the investigator as not related, possibly related, or probably related; all AEs classified as possibly or probably related were considered treatment-related.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
• Results posted on: 2021-02-23

Participant Flow

The study was conducted at 11 clinical sites in the United States and France. The study was to include a dose escalation phase to determine maximum tolerated dose (MTD) followed by expansion cohorts to further evaluate the safety and tolerability of the MTD. Enrollment was closed following enrollment of the dose escalation Cohort 4 and the expansion phase was not conducted.

Participants with advanced solid tumors, including glioma, or angioimmunoblastic T-cell lymphoma (AITL) were enrolled into sequential cohorts of increasing doses of enasidenib in the dose-escalation phase of the study.

Participant milestones

Measure	Enasidenib 100 mg Participants received enasidenib 100 mg tablets once a day (QD) on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Overall Study STARTED	3	4	7	7
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	3	4	7	7

Reasons for withdrawal

Measure	Enasidenib 100 mg Participants received enasidenib 100 mg tablets once a day (QD) on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Overall Study Progression of Disease	3	4	5	2
Overall Study Death	0	0	0	2
Overall Study Adverse Event	0	0	0	1
Overall Study Withdrawal by Subject	0	0	2	1
Overall Study Physician Decision	0	0	0	1

Baseline Characteristics

Study of Orally Administered Enasidenib (AG-221) in Adults With Advanced Solid Tumors, Including Glioma, or Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation

Baseline characteristics by cohort

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Total n=21 Participants Total of all reporting groups
Age, Continuous	56.3 years STANDARD_DEVIATION 16.80 • n=5 Participants	68.0 years STANDARD_DEVIATION 5.10 • n=7 Participants	52.0 years STANDARD_DEVIATION 18.47 • n=5 Participants	61.3 years STANDARD_DEVIATION 13.34 • n=4 Participants	58.8 years STANDARD_DEVIATION 14.97 • n=21 Participants
Age, Customized < 60 years	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Age, Customized 60 to < 70 years	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Age, Customized 70 to < 75 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Age, Customized ≥ 75 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	13 Participants n=21 Participants
Race Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race White	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Race Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1= Restricted but Ambulatory	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory but Unable to Work	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self-Care	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4 = Completely Disabled	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Tumor Type Cholangiocarcinoma	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants
Tumor Type Chondrosarcoma	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Tumor Type Glioma	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Tumor Type Angioimmunoblastic T-cell lymphoma (AITL)	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants
Tumor Type Other	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Isocitrate dehydrogenase 2 (IDH2) Mutation Type R172	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	15 Participants n=21 Participants
Isocitrate dehydrogenase 2 (IDH2) Mutation Type R140	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Isocitrate dehydrogenase 2 (IDH2) Mutation Type Other	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Isocitrate dehydrogenase 2 (IDH2) Mutation Type Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Isocitrate dehydrogenase (IDH) 1 Gene Result IDH1 R132	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Isocitrate dehydrogenase (IDH) 1 Gene Result Negative	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	16 Participants n=21 Participants
Isocitrate dehydrogenase (IDH) 1 Gene Result Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants
Isocitrate dehydrogenase (IDH) 1 Gene Result Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Body Surface Area (BSA)	1.8 m² STANDARD_DEVIATION 0.21 • n=5 Participants	2.1 m² STANDARD_DEVIATION 0.15 • n=7 Participants	1.8 m² STANDARD_DEVIATION 0.23 • n=5 Participants	1.8 m² STANDARD_DEVIATION 0.18 • n=4 Participants	1.8 m² STANDARD_DEVIATION 0.22 • n=21 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.

Population: All participants who were enrolled and received at least 1 dose of study drug

Treatment-emergent adverse events included any adverse events (AEs) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of the study drug. Severity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 or according to the following scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Fatal, death related to AE.

A serious AE is any AE occurring at any dose that:

• Resulted in death;
• Was life-threatening;
• Required or prolonged existing inpatient hospitalization;
• Resulted in persistent or significant disability/incapacity;
• Was a congenital anomaly/birth defect;
• Constituted an important medical event.

Relationship to study drug administration was determined by the investigator as not related, possibly related, or probably related; all AEs classified as possibly or probably related were considered treatment-related.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-emergent adverse event (TEAE)	3 Participants	4 Participants	6 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-related TEAE	3 Participants	4 Participants	5 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade 3/4 TEAE	2 Participants	3 Participants	5 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade 3/4 treatment-related TEAE	0 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade ≥ 3 TEAE	2 Participants	3 Participants	5 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade ≥ 3 treatment-related TEAE	0 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade 5 TEAE	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 Grade 5 treatment-related TEAE	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 serious TEAE	2 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 serious treatment-related TEAE	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 TEAE leading to discontinuation of enasidenib	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-related TEAE leading to discontinuation of enasidenib	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 TEAE leading to dose reduction of enasidenib	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-related TEAE leading to dose reduction of enasidenib	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 TEAE leading to interruption of enasidenib	0 Participants	2 Participants	3 Participants	5 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-related TEAE leading interruption of enasidenib	0 Participants	0 Participants	2 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 TEAE leading to death	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) ≥ 1 treatment-related TEAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Cycle 1 (28 days)

Population: All enrolled and treated participants

Toxicities were graded and documented according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. A dose-limiting toxicity (DLT) was defined as an event considered related to enasidenib and meeting 1 of the following criteria:

Non-hematologic:

• All clinically significant non-hematologic toxicities CTCAE ≥ Grade 3, considered not related to underlying disease or intercurrent illness, 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:

• Drug-related, prolonged myelosuppression of ≥ Grade 4 neutropenia or thrombocytopenia lasting beyond Day 28 of Cycle 1 unless related to bone marrow involvement by AITL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Number of Participants With Dose-limiting Toxicities	0 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and at end of treatment

Population: Enrolled participants with available data at each time point

ECOG performance status is used by doctors and researchers to assess how a subjects disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis.

• 0 = Fully active (most favorable activity);
• 1 = Restricted activity but ambulatory;
• 2 = Ambulatory but unable to carry out work activities;
• 3 = Limited self-care;
• 4 = Completely disabled, no self-care (least favorable activity).

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Baseline	1.3 score on a scale Standard Deviation 1.15	0.5 score on a scale Standard Deviation 0.58	0.9 score on a scale Standard Deviation 0.90	0.9 score on a scale Standard Deviation 0.90
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Cycle 1 Day 15	1.7 score on a scale Standard Deviation 0.58	1.8 score on a scale Standard Deviation 1.50	0.8 score on a scale Standard Deviation 0.84	1.0 score on a scale Standard Deviation 0.71
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Cycle 2 Day 1	1.7 score on a scale Standard Deviation 0.58	0.8 score on a scale Standard Deviation 0.50	1.2 score on a scale Standard Deviation 1.30	0.7 score on a scale Standard Deviation 0.58
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Cycle 3 Day 1	1.0 score on a scale	—	1.0 score on a scale Standard Deviation 0.00	1.0 score on a scale Standard Deviation 0.00
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Cycle 4 Day 1	1.0 score on a scale	—	1.0 score on a scale Standard Deviation 0.00	1.0 score on a scale
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit Cycle 5 Day 1	—	—	1.0 score on a scale Standard Deviation 0.00	1.0 score on a scale
Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit End of Treatment	2.5 score on a scale Standard Deviation 0.71	0.7 score on a scale Standard Deviation 0.58	1.3 score on a scale Standard Deviation 1.50	1.7 score on a scale Standard Deviation 1.15

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for assessment of enasidenib pharmacokinetics (PK).

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Enasidenib on Day -3	1403.4 ng/mL Geometric Coefficient of Variation 77.9	1433.0 ng/mL Geometric Coefficient of Variation 51.2	4540.6 ng/mL Geometric Coefficient of Variation 63.7	4702.9 ng/mL Geometric Coefficient of Variation 61.3

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for assessment of enasidenib pharmacokinetics (PK).

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Time of Maximum Plasma Concentration (Tmax) of Enasidenib After a Single Dose on Day -3	2.0 hours Interval 2.0 to 8.0	6.1 hours Interval 2.0 to 25.0	8.0 hours Interval 2.0 to 10.0	3.3 hours Interval 2.0 to 24.0

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for assessment of enasidenib pharmacokinetics (PK).

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration Time Curve From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After a Single Oral Dose on Day -3	10031.7 h*ng/mL Geometric Coefficient of Variation 79.0	11040.2 h*ng/mL Geometric Coefficient of Variation 55.9	31959.0 h*ng/mL Geometric Coefficient of Variation 56.7	29847.8 h*ng/mL Geometric Coefficient of Variation 59.6

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for assessment of enasidenib pharmacokinetics (PK).

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 72 hours post-dose (AUC0-72) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration Time Curve From Time Zero to 72 Hours Postdose (AUC0-72) of Enasidenib After a Single Dose on Day -3	62420.0 h*ng/mL Geometric Coefficient of Variation 80.6	86900.7 h*ng/mL Geometric Coefficient of Variation 62.5	206214.4 h*ng/mL Geometric Coefficient of Variation 65.2	248315.9 h*ng/mL Geometric Coefficient of Variation 69.9

SECONDARY outcome

Timeframe: Day -3 pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3	94.2 ng/mL Geometric Coefficient of Variation 64.5	71.9 ng/mL Geometric Coefficient of Variation 70.8	273.0 ng/mL Geometric Coefficient of Variation 52.9	239.4 ng/mL Geometric Coefficient of Variation 64.8

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3	70.3 hours Interval 8.0 to 74.0	71.7 hours Interval 71.0 to 73.0	71.7 hours Interval 2.0 to 73.0	72.0 hours Interval 48.0 to 72.0

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=5 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3	518.6 h*ng/mL Geometric Coefficient of Variation 64.5	233.3 h*ng/mL Geometric Coefficient of Variation 30.6	1358.2 h*ng/mL Geometric Coefficient of Variation 46.5	965.2 h*ng/mL Geometric Coefficient of Variation 67.8

SECONDARY outcome

Timeframe: Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters.

The first 3 to 5 participants enrolled in each cohort in the dose escalation phase received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 72 hours post-dose (AUC0-72) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=2 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=1 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose (AUC0-72) for AGI-16903 After a Single Dose of Enasidenib on Day -3	7556.4 h*ng/mL Geometric Coefficient of Variation 42.9	7294.2 h*ng/mL Geometric Coefficient of Variation 99999	13752.5 h*ng/mL Geometric Coefficient of Variation 57.8	12519.5 h*ng/mL Geometric Coefficient of Variation 74.7

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=2 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=2 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=3 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Enasidenib After Multiple Doses	106522.9 h*ng/mL Geometric Coefficient of Variation 46.7	161862.9 h*ng/mL Geometric Coefficient of Variation 1.4	154248.7 h*ng/mL Geometric Coefficient of Variation 33.3	221865.0 h*ng/mL Geometric Coefficient of Variation 10.1

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Maximum Observed Plasma Concentration (Cmax) of Enasidenib After Multiple Doses	10717.9 ng/mL Geometric Coefficient of Variation 54.1	14945.4 ng/mL Geometric Coefficient of Variation 40.4	19401.1 ng/mL Geometric Coefficient of Variation 39.9	29316.3 ng/mL Geometric Coefficient of Variation 7.1

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Time of Maximum Plasma Concentration (Tmax) of Enasidenib After Multiple Doses	8.0 hours Interval 6.0 to 10.0	5.9 hours Interval 1.0 to 10.0	2.0 hours Interval 1.0 to 2.0	2.2 hours Interval 2.0 to 8.0

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=2 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=3 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Metabolite AGI-16903 After Multiple Doses of Enasidenib	9074.5 h*ng/mL Geometric Coefficient of Variation 53.6	13914.2 h*ng/mL Geometric Coefficient of Variation 13.2	19865.8 h*ng/mL Geometric Coefficient of Variation 36.8	23007.5 h*ng/mL Geometric Coefficient of Variation 34.8

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib	1093.7 ng/mL Geometric Coefficient of Variation 59.5	1435.7 ng/mL Geometric Coefficient of Variation 29.9	2101.1 ng/mL Geometric Coefficient of Variation 56.7	2837.0 ng/mL Geometric Coefficient of Variation 31.6

SECONDARY outcome

Timeframe: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose.

Population: Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters.

AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib	8.0 hours Interval 2.0 to 10.0	5.9 hours Interval 1.0 to 10.0	1.4 hours Interval 1.0 to 2.0	2.2 hours Interval 2.0 to 8.0

SECONDARY outcome

Timeframe: Response assessments were performed every 56 days up to the end of treatment; median (minimum, maximum) duration of treatment was 50.0 (34, 112), 51.5 (41, 57), 40.0 (4, 170), and 27.0 (3, 126) days in each treatment group respectively.

Population: Enrolled participants with solid tumors (excluding glioma) who received at least 1 dose of study drug.

Response was assessed based on radiographic evaluations according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria for participants with solid tumors without glioma.

An objective response was defined as the percentage of participants with complete response (CR) or partial response (PR), confirmed no less than 4 weeks after the criteria for response were first met based on RECIST 1.1.

Complete response: Disappearance of all target and non-target lesions, pathological lymph nodes must have reduction in short axis to < 10 mm, and no new lesions.

Partial response: Disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker levels above the normal limits, or, at least a 30% decrease in the size of target lesions and no progression of existing non-target lesions and no new lesions.

Outcome measures

Measure	Enasidenib 100 mg n=1 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=3 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=3 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants With Solid Tumors (Excluding Glioma) Who Achieved an Objective Response	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Response assessments were performed every 56 days up to the end of treatment; median (minimum, maximum) duration of treatment was 50.0 (34, 112), 51.5 (41, 57), 40.0 (4, 170), and 27.0 (3, 126) days in each treatment group respectively.

Population: Enrolled participants with glioma who received at least 1 dose of study drug.

Response was assessed based on modified Response Assessment in Neuro-Oncology (RANO) working group criteria in participants with glioma.

An objective response is defined as the percentage of participants with a CR or PR, confirmed no less than 4 weeks based on the modified RANO) criteria.

CR: Complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks, stable or improved non-enhancing (T2/FLAIR) lesions, no new lesions, participants must be off corticosteroids (or on physiologic replacement doses only), and clinically stable or improved.

PR: At least 50% decrease compared to Baseline in the size of all measurable enhancing lesions sustained for at least 4 weeks, no progression of non-measurable disease or any new lesions, stable of lower dose of corticosteroids than Baseline dose, and stable or improved non-enhancing (T2/FLAIR) lesions.

Outcome measures

Measure	Enasidenib 100 mg n=1 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=4 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=1 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants With Glioma Who Achieved an Objective Response	0 percentage of participants	—	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Response assessments were performed every 56 days up to the end of treatment; median (minimum, maximum) duration of treatment was 50.0 (34, 112), 51.5 (41, 57), 40.0 (4, 170), and 27.0 (3, 126) days in each treatment group respectively.

Population: Enrolled participants with AITL who received at least 1 dose of study drug.

Response assessments for participants with AITL were based on the revised International Working Group (IWG) Response criteria for Malignant Lymphoma. Overall response was defined as the percentage of participants who achieved a CR or PR based on IWG criteria.

CR: Disappearance of all evidence of disease, including nodal masses, extra nodal masses, and bone marrow.

PR: Regression of measurable disease and no new sites (≥ 50% decrease in size from Baseline of all index lesions (both nodal and extranodal lesions), no obvious increase in non-index lesions/disease, fludeoxyglucose (FDG)-avid or positron emission tomography (PET) positive prior to therapy; one or more PET positive at previously involved site, variably FDG-avid or PET negative; regression on computed tomography (CT), no increase in size of liver or spleen).

Outcome measures

Measure	Enasidenib 100 mg n=1 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=1 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=3 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Percentage of Participants With AITL Who Achieved an Objective Response	0 percentage of participants	0 percentage of participants	—	0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Cycle 1 Days 1, 8, 15, and 22, Cycle 2 Days 1 and 15 and Day 1 of every cycle thereafter.

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

QT interval was measured by electrocardiogram throughout the study. The maximum increase in QTcF from Baseline observed across all assessments is reported according to the following categories: increase ≤ 30 milliseconds (ms), increase > 30 to ≤ 60 ms, and increase > 60 ms.

Outcome measures

Measure	Enasidenib 100 mg n=3 Participants Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 Participants Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=6 Participants Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 Participants Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category QTcF Increased from Baseline ≤ 30 ms	3 Participants	1 Participants	5 Participants	5 Participants
Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category QTcF Increased from Baseline > 30 to ≤ 60 ms	0 Participants	3 Participants	0 Participants	0 Participants
Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category QTcF Increased from Baseline > 60 ms	0 Participants	0 Participants	0 Participants	1 Participants
Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category Missing	0 Participants	0 Participants	1 Participants	0 Participants
Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category no QTcF Increase from Baseline	0 Participants	0 Participants	0 Participants	1 Participants

Adverse Events

Enasidenib 100 mg

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Enasidenib 200 mg

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Enasidenib 400 mg

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Enasidenib 650 mg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 2 deaths

Serious adverse events

Measure	Enasidenib 100 mg n=3 participants at risk Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 participants at risk Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 participants at risk Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 participants at risk Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Mental status changes	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Apnoea	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 5 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Vascular disorders Hypotension	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Myocardial infarction	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Sinus tachycardia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Nausea	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Vomiting	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Death	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Disease progression	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Pyrexia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Lung infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Sepsis	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Septic shock	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Muscle enzyme increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.

Other adverse events

Measure	Enasidenib 100 mg n=3 participants at risk Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 200 mg n=4 participants at risk Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 400 mg n=7 participants at risk Participants received enasidenib 400 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.	Enasidenib 650 mg n=7 participants at risk Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
Nervous system disorders Hemiparesis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Lethargy	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Headache	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Facial paresis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Metabolic encephalopathy	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Somnolence	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Partial seizures	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Acute coronary syndrome	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Palpitations	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Angina pectoris	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Sinus tachycardia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Supraventricular tachycardia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Cardiac disorders Tachycardia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Eye disorders Conjunctivitis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Eye disorders Dry eye	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Constipation	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	57.1% 4/7 • Number of events 7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Dysphagia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Flatulence	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	50.0% 2/4 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	71.4% 5/7 • Number of events 7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	57.1% 4/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Salivary hypersecretion	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Gastrointestinal disorders Vomiting	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Asthenia	66.7% 2/3 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Chills	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Fatigue	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	75.0% 3/4 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	57.1% 4/7 • Number of events 6 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Gait disturbance	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Malaise	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Non-cardiac chest pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Oedema peripheral	33.3% 1/3 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
General disorders Pyrexia	33.3% 1/3 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Hepatobiliary disorders Hepatocellular injury	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Hepatobiliary disorders Jaundice	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Bacteraemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Helicobacter infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Herpes simplex	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Lung infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Oral infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Oral candidiasis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Pharyngitis	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Septic shock	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Skin bacterial infection	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Infections and infestations Urinary tract infection	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Wound	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Shunt malfunction	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Injury, poisoning and procedural complications Wound complication	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Alanine aminotransferase increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Amylase increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Bilirubin conjugated increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood alkaline phosphatase increased	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood bilirubin increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 11 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood bilirubin unconjugated increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood creatine phosphokinase increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood creatinine increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	50.0% 2/4 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood fibrinogen decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood lactate dehydrogenase increased	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Blood urea increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Ejection fraction decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Haematocrit decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Hepatic enzyme increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations International normalised ratio increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Lipase decreased	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Lymphocyte count decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Platelet count decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Troponin increased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Investigations Weight decreased	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Decreased appetite	66.7% 2/3 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hyperglycaemia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	50.0% 2/4 • Number of events 4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypoalbuminaemia	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	50.0% 2/4 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Costochondritis	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Osteonecrosis	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Dizziness	33.3% 1/3 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Syncope	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Nervous system disorders Tremor	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Agitation	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Anxiety	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Confusional state	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Delirium	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Psychiatric disorders Insomnia	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	42.9% 3/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Renal and urinary disorders Dysuria	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Reproductive system and breast disorders Scrotal erythema	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Apnoea	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Cough	66.7% 2/3 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	28.6% 2/7 • Number of events 3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Dyspnoea	66.7% 2/3 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 2 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Tachypnoea	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Acne	33.3% 1/3 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Butterfly rash	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	25.0% 1/4 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Vascular disorders Hypertension	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Vascular disorders Hypotension	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Vascular disorders Venous thrombosis limb	0.00% 0/3 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/4 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	14.3% 1/7 • Number of events 1 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.	0.00% 0/7 • From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email:

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is \> 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
• Publication restrictions are in place

Restriction type: OTHER