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

Toxicity severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT was defined as: • Non-hematologic toxicities: CTCAE ≥ Grade 3 with the exception of ≥ Grade 3 blood bilirubin increases in participants with a uridine diphosphate- glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) mutation. In participants with a UGT1A1 mutation, blood bilirubin increases of \> 5× upper limit of normal (ULN) were considered a DLT. • Hematologic toxicities: Prolonged myelosuppression, defined as persistence of ≥ Grade 3 neutropenia or thrombocytopenia (by NCI CTCAE v4.03), leukemia-specific criteria, i.e., marrow cellularity \<5% on Day 28 or later from the start of study drug without evidence of leukemia) at least 42 days after the initiation of Cycle 1 therapy. Leukemia-specific grading was used for cytopenias (based on percentage decrease from Baseline: 50 to 75% = Grade 3, \>75% = Grade 4)

Time frame: From time of first dose up to the end of Cycle 1; 28 days

Population: All participants who took at least one dose of study drug in the dose escalation phase and either had a DLT during Cycle 1, regardless of the amount of study drug exposure, or had no DLT and completed at least 75% of their planned Cycle 1 doses, and were considered to have had enough safety data to conclude that a DLT did not occur during Cycle 1.

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Requires inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time frame: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff date of 01 September 2017; median treatment duration in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).

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

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Required inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time frame: From the first dose of investigational product (IP) up to 28 days after the last dose of IP up to the data cutoff date of 01 September 2017; median treatment duration in Part 1 Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: All participants in Phase 1 Expansion who received at least 1 dose of study treatment.

ORR is defined as the percentage of participants achieving an overall response of complete response (CR), CR with incomplete neutrophil recovery (CRi), CR with incomplete platelet recovery (CRp), partial response (PR), or morphologic leukemia-free state (MLFS) based on the 2003 revised International Working Group (IWG) criteria for AML, assessed by the Investigator. CR: • Absolute neutrophil count (ANC) \> 1.0 x10⁹/L • Platelet count \> 100 x10⁹/L • Bone marrow (BM) blasts \< 5% • Absence of blasts with Auer rods • Independence of red cell transfusions CRi: • All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: • All CR criteria except for residual thrombocytopenia (platelets \< 100 x 10⁹/L) PR: • Meets hematologic criteria of CR • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: • Bone marrow blasts \< 5% • Absence of blasts with Auer rods • Absence of extramedullary disease • No hematologic recovery required

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time frame: From the first dose of investigational product (IP) up to 28 days after the last dose, up to the data cutoff of date of 01 September 2017; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment

A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).

Time frame: From the primary analysis cut-off date of 01 September 2017 to the final analysis cut-off date of 29 July 2019, a maximum of 23 months.

Population: Participants who received at least 1 dose of study treatment during the Safety Follow-up Period.

For participants with R/R AML ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML. CR: - ANC \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CRi: - All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: - All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L) PR: - Meets hematologic criteria of CR - Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: - Bone marrow blasts \< 5% - Absence of blasts with Auer rods - Absence of extramedullary disease - No hematologic recovery required

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure for Phase 1 and 2 R/R AML participants was 5.4 months (range 0.4 to 34.2 months).

Population: All participants in Phase 1 and 2 with R/R AML who received at least one dose of study treatment.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis. 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.

Time frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Day -3 or Cycle 1, Day 1 and Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took \< 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. Participants in Phase 1 and 2 who received enasidenib 100 mg QD are combined for the analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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. t1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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. T1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Dose Expansion 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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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 the time of the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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 hour 8 post-dose (AUC 0-8) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose.

Population: Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation and Expansion cohorts were were grouped by dose for Day -3 analyses.

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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

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

Population: Participants who received enasidenib on Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

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

Population: Participants who received enasidenib on Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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 the time of the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

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 the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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 the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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

Time frame: Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).

Population: The population included all participants who received at least one dose of study treatment in Phase 1 Dose Escalation and Dose Expansion. Results were analyzed and are reported for Phase 1 combined.

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

Time frame: Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months).

Population: The population included all participants who received at least one dose of study treatment in Phase 1 Dose Escalation and Dose Expansion. Results were analyzed and are reported for Phase 1 combined.

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator. CR for AML: - Absolute neutrophil count (ANC) \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CR for MDS: - Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines - Peripheral blood: -- Hemoglobin ≥ 11 g/dL -- Platelets ≥ 100 × 10⁹/L -- Neutrophils ≥ 1.0 × 10⁹/L -- Blasts = 0%

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).

Population: All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.

ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, marrow CR (mCR) (for MDS) and MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS. CR: • ANC \> 1.0 x10⁹/L • Platelet count \> 100 x10⁹/L • Bone marrow (BM) blasts \< 5% • Absence of blasts with Auer rods • Independence of red cell transfusions CRi: • All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: • All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L) PR: • Meets hematologic criteria of CR • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: • Bone marrow blasts \< 5% • Absence of blasts with Auer rods • Absence of extramedullary disease • No hematologic recovery required mCR: • Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months).

Population: All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp), based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator review. CR: - ANC \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CRi: - All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: - All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L)

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).

Population: All participants who received at least one dose of study treatment in Phase 1 Dose Escalation. Participants were grouped according to assigned total daily dose.

Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, mCR (for MDS) / MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Escalation and who had an objective response. Participants were grouped according to assigned total daily dose.

Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation phase was 5.0 months (range 0.4 to 34.2 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Escalation with a complete response. Participants were grouped according to assigned total daily dose.

Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, mCR (for MDS) or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS as assessed by the Investigator.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Escalation who had an objective response. Participants were grouped according to assigned total daily dose.

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator. CR for AML: - Absolute neutrophil count (ANC) \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CR for MDS: - Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines - Peripheral blood: -- Hemoglobin ≥ 11 g/dL -- Platelets ≥ 100 × 10⁹/L -- Neutrophils ≥ 1.0 × 10⁹/L -- Blasts = 0%

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.

ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, mCR (for MDS), or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS. CR: - ANC \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CRi: - All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: - All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L) PR: - Meets hematologic criteria of CR - Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: - Bone marrow blasts \< 5% - Absence of blasts with Auer rods - Absence of extramedullary disease - No hematologic recovery required mCR: - Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: All participants who received at least one dose of study treatment in Phase 1 Expansion.

Among participants who had a response of CR based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS assessed by the Investigator, duration of complete response was calculated from the date of the first occurrence of complete response to the date of documented disease relapse, progression or death, whichever occurred earlier. DOCR was estimated using the Kaplan-Meier method. Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Expansion with a complete response.

Among participants who had a response of CR, CRi, CRp, PR, mCR, or MLFS based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method. Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Expansion with an objective response.

Event-free survival is defined as the interval from the date of the first dose to the date of documented relapse, progression, or death due to any cause, whichever occurs first. Participants without an EFS event were censored at the date of the last adequate response assessment.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).

Population: All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.

Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months).

Population: All participants in Phase 1 Dose Expansion who received at least one dose of study treatment.

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the investigator. CR: - ANC \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CRi: - All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: - All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L)

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: All participants who received at least one dose of study treatment in Phase 1 Dose Expansion.

Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, mCR (for MDS) / MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Expansion who had an objective response.

Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Expansion who had a complete response.

Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, mCR (for MDS) or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS as assessed by the Investigator.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months).

Population: Participants who received at least one dose of study treatment in Phase 1 Dose Expansion who had an objective response.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). Plasma 2-HG was measured using qualified LC-MS/MS in order to characterize the pharmacodynamic (PD) effects of enasidenib; the LLOQ was 30.0 ng/mL. Minimum percent change from Baseline response value post-dose over 10 hours was calculated as: (minimum observed concentration post-dose over 10 hours \[Rmin\] - Baseline) / Baseline \* 100. Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values. Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.

Time frame: Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 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 PD parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Dose Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL. Minimum percent change from Baseline response value post-dose over 10 hours was calculated as: (minimum observed concentration post-dose over 10 hours \[Rmin\] - Baseline) / Baseline \* 100. Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values. Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.

Time frame: Cycle 1, Day 15 and 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). Plasma 2-HG was measured using qualified LC-MS/MS in order to characterize the pharmacodynamic (PD) effects of enasidenib; the LLOQ was 30.0 ng/mL. Area under the effect concentration time curve from time point zero (predose) up to 10 hours postdose (AUEC0-10) was calculated using the linear trapezoid rule. Percent change from Baseline for AUEC0-10 was calculated as (AUEC0-10 minus \[Baseline\*Tlast\]) / (Baseline\*Tlast) \* 100, where Tlast corresponded to 10 hours and Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values. Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.

Time frame: Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 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 PD parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL. Area under the effect concentration time curve from time point zero (predose) up to 10 hours postdose (AUEC0-10) was calculated using the linear trapezoid rule. Percent change from baseline for AUEC0-10 was calculated as: (AUEC0-10 minus \[Baseline\*Tlast\]) / (Baseline\*Tlast) \* 100, where Tlast corresponded to 10 hours and Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values. Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.

Time frame: Cycle 1, Day 15 and 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL.

Time frame: Cycle 1, Day 15 and 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 1, Day 15 or Cycle 2, Day 1 with sufficient data to determine PD parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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 PD parameters. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3). 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.

Time frame: Day -3 prior to the single dose of enasidenib and at 0.5, 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. Participants who received 2 doses on Day -3 or who received the incorrect dose were excluded. Participants in the Phase 1 Escalation BID and QD cohorts and Phase 1 Expansion cohorts were were grouped by dose for Day -3 analyses.

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.

Time frame: 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. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis. Participants in the Phase 1 Escalation and Expansion Enasidenib 100 mg QD cohorts were combined for analysis.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1. T1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2 Day 1. t1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.

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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2 Day 1.

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 8 hours post-dose (AUC0-8) of enasidenib was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

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 the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2 Day 1.

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 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

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 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

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 the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML as assessed by the investigator. CR for AML: - Absolute neutrophil count (ANC) \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

Among participants who had a response of CR based on the 2003 revised IWG criteria for AML assessed by the Investigator, duration of complete response was calculated from the date of the first occurrence of complete response to the date of documented disease relapse, progression or death, whichever occurred earlier. DOCR was estimated using the Kaplan-Meier method. Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).

Population: Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had a complete response.

For participants with an objective response based on the 2003 revised IWG criteria for AML assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. Participants without relapse, progressive disease or death were censored at the last response assessment date. Relapse (for participants who previously attained CR, Cri, CRp or MLFS): BM blasts ≥ 5%, reappearance of blasts in the blood or development of extramedullary disease. Disease progression (for participants who previously attained PR): development of new extramedullary disease, or For participants with 5% to 67% BM blasts at nadir: - a \> 50% increase in BM blasts from nadir and that is ≥ 20%. For participants with ≥ 67% BM blasts at nadir: - a doubling of the nadir absolute peripheral blood (PB) blast count and the final absolute PB blast count \> 10 x 10⁹/L.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).

Population: Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had an objective response.

Event-free survival is defined as the interval from the date of the first dose to the date of documented relapse, progression, or death due to any cause, whichever occurred first. Participants without an EFS event were censored at the date of the last adequate response assessment.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.

Time frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML, assessed by the Investigator. CR: - ANC \> 1.0 x10⁹/L - Platelet count \> 100 x10⁹/L - Bone marrow (BM) blasts \< 5% - Absence of blasts with Auer rods - Independence of red cell transfusions CRi: - All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: - All CR criteria except for residual thrombocytopenia (platelet counts \< 100 x 10⁹/L)

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had an objective response.

Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML per investigator assessment.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had a complete response.

Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML as assessed by the Investigator.

Time frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: Participants in Phase 2 with R/R AML who received at least one dose of study treatment and who had an objective response.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2 Day 1.

Participants who achieved 56-day post-baseline platelet transfusion independence, i.e. with no platelet transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline platelet transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.

Time frame: Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

Participants who achieved 56-day post-baseline red blood cell (RBC) transfusion independence, i.e. with no RBC transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline RBC transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.

Time frame: Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months).

Population: All participants In Phase 2 with R/R AML who received at least 1 dose of study treatment.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1, Day 1 or Cycle 2, Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2, Day 1.

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.

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose.

Population: Participants who received enasidenib on Cycle 1 Day 1 or Cycle 2 Day 1 with sufficient data to determine PK parameters. Participants who took less than 80% of their planned continuous dosing regimen were excluded from the analysis of Cycle 2 Day 1.