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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003424-47 | EudraCT Number |
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| Name | Class |
|---|---|
| Celgene Corporation | INDUSTRY |
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The purpose of this study is to evaluate the safety, pharmacokinetics, and clinical activity of enasidenib in adults with advanced solid tumors, including glioma, or with angioimmunoblastic T-cell lymphoma (AITL), with an isocitrate dehydrogenase-2 (IDH2) mutation.
The first portion of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of enasidenib to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose. The second portion of the study is a planned dose expansion phase where three cohorts of patients will receive enasidenib to further evaluate the safety, tolerability, and clinical activity. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Enrollment into the AG221-C-003 study was closed following enrollment of the dose escalation Cohort 4 (650 mg QD) in order to focus resources on the development of other pipeline IDH inhibitors in solid tumors, gliomas, and lymphoma; it was not due to safety reasons. Participants receiving enasidenib at the time of study closure were to be allowed to continue treatment until disease progression or the development of unacceptable toxicity, as outlined in the study protocol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enasidenib | Experimental | During the dose escalation phase, consented eligible participants will be enrolled into sequential cohorts of increasing doses of enasidenib.The starting dose for this study is 100 mg administered every 24 hours, |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enasidenib | Drug | Enasidenib tablets administered orally once a day in 28-day treatment cycles until disease progression or unacceptable toxicities. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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:
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. | From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts. |
| Number of Participants With Dose-limiting Toxicities | 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. | Cycle 1 (28 days) |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Enasidenib on Day -3 | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category | 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. | Baseline, Cycle 1 Days 1, 8, 15, and 22, Cycle 2 Days 1 and 15 and Day 1 of every cycle thereafter. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development | Agios Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | 90095 | United States | |||
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Enasidenib 200 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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.
| 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 |
| Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| Time of Maximum Plasma Concentration (Tmax) of Enasidenib After a Single Dose on Day -3 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| 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 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| 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 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 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. | Day -3 pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| 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 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| 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 | 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. | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Enasidenib After Multiple Doses | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Enasidenib After Multiple Doses | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| Time of Maximum Plasma Concentration (Tmax) of Enasidenib After Multiple Doses | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| 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 | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 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. | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| Percentage of Participants With Solid Tumors (Excluding Glioma) Who Achieved an Objective Response | 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. | 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. |
| Percentage of Participants With Glioma Who Achieved an Objective Response | 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. | 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. |
| Percentage of Participants With AITL Who Achieved an Objective Response | 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). | 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. |
| Los Angeles |
| California |
| 91010 |
| United States |
| Miami | Florida | 33136 | United States |
| Baltimore | Maryland | 21287 | United States |
| Boston | Massachusetts | 02114 | United States |
| Omaha | Nebraska | 68198 | United States |
| New York | New York | 10065 | United States |
| Cleveland | Ohio | 44195 | United States |
| Nashville | Tennessee | 37203 | United States |
| Dallas | Texas | 75390 | United States |
| Bordeaux | 61283 33076 | France |
| Villejuif | 94805 | France |
Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
| FG002 | 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. |
| FG003 | 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. |
| COMPLETED | Participants ongoing treatment |
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| NOT COMPLETED |
|
|
All enrolled particpants
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| ID | Title | Description |
|---|---|---|
| BG000 | Enasidenib 100 mg | Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race | Count of Participants | Participants |
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| Eastern Cooperative Oncology Group (ECOG) Performance Status | 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.
| Count of Participants | Participants |
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| Tumor Type | Count of Participants | Participants |
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| Isocitrate dehydrogenase 2 (IDH2) Mutation Type | Isocitrate dehydrogenase 2 (IDH2) gene mutations have been described in patients with gliomas, chondrosarcomas, intrahepatic cholangiocarcinomas, as well as a variety of other solid and liquid tumors. Mutations in IDH2 most commonly lead to alterations affecting arginine-172 (R172) or arginine-140 (R140) in IDH2. The mutated protein shows a gain-of-function, neomorphic activity, catalyzing the reduction of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), an oncogenic metabolite. Mutation in IDH2 was required for study entry. | Count of Participants | Participants |
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| Isocitrate dehydrogenase (IDH) 1 Gene Result | IDH1 mutations have been found in those with both blood and solid tumors; mutations in IDH1 and IDH2 are almost always mutually exclusive and occur at very early stages of tumor development suggesting that they promote formation and progression of tumors. Mutations in the IDH1 protein most commonly lead to alterations affecting arginine-132 (R132H or R132C) | Count of Participants | Participants |
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| Body Surface Area (BSA) | BSA is the total surface area of the body. BSA was calculated as weight (kilograms)^0.425 x height (cm)^0.725 / 139.2. | Mean | Standard Deviation | m² |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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:
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. | All participants who were enrolled and received at least 1 dose of study drug | Posted | Count of Participants | Participants | From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts. |
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| Primary | Number of Participants With Dose-limiting Toxicities | 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. | All enrolled and treated participants | Posted | Count of Participants | Participants | Cycle 1 (28 days) |
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| Primary | Eastern Cooperative Oncology Group (ECOG) Performance Status at Each Visit | 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.
| Enrolled participants with available data at each time point | Posted | Mean | Standard Deviation | score on a scale | 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 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Enasidenib on Day -3 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | Time of Maximum Plasma Concentration (Tmax) of Enasidenib After a Single Dose on Day -3 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Median | Full Range | hours | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | 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 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
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| Secondary | 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 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day -3 pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters | Posted | Median | Full Range | hours | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | 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 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | Participants who received 1 dose of enasidenib on Day -3 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day -3, pre-dose and at 30 minutes and 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Enasidenib After Multiple Doses | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Enasidenib After Multiple Doses | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
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| Secondary | Time of Maximum Plasma Concentration (Tmax) of Enasidenib After Multiple Doses | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Median | Full Range | hours | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 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. | Participants who received enasidenib on Cycle 2 Day 1 with sufficient data to determine PK parameters. | Posted | Median | Full Range | hours | Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. |
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| Secondary | Percentage of Participants With Solid Tumors (Excluding Glioma) Who Achieved an Objective Response | 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. | Enrolled participants with solid tumors (excluding glioma) who received at least 1 dose of study drug. | Posted | Number | percentage of participants | 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. |
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| Secondary | Percentage of Participants With Glioma Who Achieved an Objective Response | 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. | Enrolled participants with glioma who received at least 1 dose of study drug. | Posted | Number | percentage of participants | 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. |
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| Secondary | Percentage of Participants With AITL Who Achieved an Objective Response | 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). | Enrolled participants with AITL who received at least 1 dose of study drug. | Posted | Number | percentage of participants | 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. |
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| Other Pre-specified | Maximum Increase From Baseline in Corrected QT Interval Based on Fridericia's Formula (QTcF) by Category | 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. | Enrolled participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline, Cycle 1 Days 1, 8, 15, and 22, Cycle 2 Days 1 and 15 and Day 1 of every cycle thereafter. |
|
From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Enasidenib 100 mg | Participants received enasidenib 100 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity. | 1 | 3 | 2 | 3 | 3 | 3 |
| EG001 | 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. | 0 | 4 | 2 | 4 | 4 | 4 |
| EG002 | 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. | 1 | 7 | 3 | 7 | 6 | 7 |
| EG003 | 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. | 2 | 7 | 4 | 7 | 7 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Muscle enzyme increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hepatocellular injury | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Oral infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Skin bacterial infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Shunt malfunction | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Wound complication | Injury, poisoning and procedural complications | MedDRA 16.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood bilirubin unconjugated increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood fibrinogen decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Haematocrit decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Lipase decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Troponin increased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 16.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Facial paresis | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Metabolic encephalopathy | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Scrotal erythema | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Butterfly rash | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
| |
| Venous thrombosis limb | Vascular disorders | MedDRA 16.0 | Systematic Assessment |
|
The study was to be conducted in 2 parts: a dose-escalation and an expansion phase. Enrollment was closed after entry into Cohort 4 to focus resources on the development of other pipeline IDH inhibitors in other tumors; there were no safety concerns.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Please email: | Clinical.Trials@bms.com |
| ID | Term |
|---|---|
| D005910 | Glioma |
| D007119 | Immunoblastic Lymphadenopathy |
| D018281 | Cholangiocarcinoma |
| D002813 | Chondrosarcoma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D000072281 | Lymphadenopathy |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D012509 | Sarcoma |
Not provided
Not provided
| ID | Term |
|---|---|
| C000605269 | enasidenib |
Not provided
Not provided
Not provided
| 60 to < 70 years |
|
| 70 to < 75 years |
|
| ≥ 75 years |
|
| Male |
|
| White |
|
| Not Reported |
|
| 1= Restricted but Ambulatory |
|
| 2 = Ambulatory but Unable to Work |
|
| 3 = Limited Self-Care |
|
| 4 = Completely Disabled |
|
| Chondrosarcoma |
|
| Glioma |
|
| Angioimmunoblastic T-cell lymphoma (AITL) |
|
| Other |
|
| R140 |
|
| Other |
|
| Missing |
|
| Negative |
|
| Other |
|
| Missing |
|
| ≥ 1 treatment-related TEAE |
|
| ≥ 1 Grade 3/4 TEAE |
|
| ≥ 1 Grade 3/4 treatment-related TEAE |
|
| ≥ 1 Grade ≥ 3 TEAE |
|
| ≥ 1 Grade ≥ 3 treatment-related TEAE |
|
| ≥ 1 Grade 5 TEAE |
|
| ≥ 1 Grade 5 treatment-related TEAE |
|
| ≥ 1 serious TEAE |
|
| ≥ 1 serious treatment-related TEAE |
|
| ≥ 1 TEAE leading to discontinuation of enasidenib |
|
| ≥ 1 treatment-related TEAE leading to discontinuation of enasidenib |
|
| ≥ 1 TEAE leading to dose reduction of enasidenib |
|
| ≥ 1 treatment-related TEAE leading to dose reduction of enasidenib |
|
| ≥ 1 TEAE leading to interruption of enasidenib |
|
| ≥ 1 treatment-related TEAE leading interruption of enasidenib |
|
| ≥ 1 TEAE leading to death |
|
| ≥ 1 treatment-related TEAE leading to death |
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG003 | 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. |
|
|
| Enasidenib 650 mg |
Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
| Enasidenib 650 mg |
Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
Participants received a single oral dose of enasidenib 400 mg on Day -3.
| OG003 | Enasidenib 650 mg | Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
Participants received a single oral dose of enasidenib 400 mg on Day -3.
| OG003 | Enasidenib 650 mg | Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
| OG003 |
| Enasidenib 650 mg |
Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
| Enasidenib 650 mg |
Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
Participants received a single oral dose of enasidenib 400 mg on Day -3.
| OG003 | Enasidenib 650 mg | Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
Participants received a single oral dose of enasidenib 400 mg on Day -3.
| OG003 | Enasidenib 650 mg | Participants received a single oral dose of enasidenib 650 mg on Day -3. |
|
|
| OG003 | 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. |
|
|
| 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. |
|
|
Participants received enasidenib 650 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity. |
|
|
| OG003 | 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. |
|
|
| OG003 |
| 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. |
|
|
| 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. |
|
|
| 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity. |
| OG002 | 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. |
| OG003 | 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. |
|
|
Participants received enasidenib 200 mg tablets QD on Days 1 to 28 of each 28-day treatment cycle until disease progression or unacceptable toxicity.
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG003 | 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. |
|
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