A Phase 1/2 interventional study of Enasidenib in Solid Tumor, Glioma and Angioimmunoblastic T-cell Lymphoma, sponsored by Celgene. Completed at 12 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-02-23.
Sponsored by Celgene (part of Bristol-Myers Squibb) · Phase 1/2, Interventional, and Treatment
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.
1,452 studies on the registry are indexed under Glioma; 349 are open to participants now.
This study's enrollment of 21 is below the median of 32 across 1,075 interventional studies indexed under Glioma.
Browse Glioma studies →Celgene is the lead sponsor of 428 studies on the registry; 12 are open to participants now.
Of its 104 completed or terminated interventional studies of FDA-regulated products, 30 (29%) have results posted.
First submitted before Celgene became part of Bristol-Myers Squibb.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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,
Drug: Enasidenib
Enasidenib tablets administered orally once a day in 28-day treatment cycles until disease progression or unacceptable toxicities.
Also known as: AG-221, IDHIFA®
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: * Resulted in death; * Was life-threatening; * Required or prolonged existing inpatient hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. Relationship to study drug administration was determined by the investigator as not related, possibly related, or probably related; all AEs classified as possibly or probably related were considered treatment-related.
Time frame: From first 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.
Time frame: Cycle 1 (28 days)
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. * 0 = Fully active (most favorable activity); * 1 = Restricted activity but ambulatory; * 2 = Ambulatory but unable to carry out work activities; * 3 = Limited self-care; * 4 = Completely disabled, no self-care (least favorable activity).
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
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.
Time frame: Baseline, Cycle 1 Days 1, 8, 15, and 22, Cycle 2 Days 1 and 15 and Day 1 of every cycle thereafter.
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.
| Milestone | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Started | 3 | 4 | 7 | 7 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 3 | 4 | 7 | 7 |
| Withdrew: Progression of disease | 3 | 4 | 5 | 2 |
| Withdrew: Death | 0 | 0 | 0 | 2 |
| Withdrew: Adverse event | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 1 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 |
Treatment-emergent adverse events included any adverse events (AEs) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of the study drug. Severity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 or according to the following scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Fatal, death related to AE. A serious AE is any AE occurring at any dose that: * Resulted in death; * Was life-threatening; * Required or prolonged existing inpatient hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly/birth defect; * Constituted an important medical event. Relationship to study drug administration was determined by the investigator as not related, possibly related, or probably related; all AEs classified as possibly or probably related were considered treatment-related.
| Participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| ≥ 1 treatment-emergent adverse event (TEAE) | 3 | 4 | 6 | 7 |
| ≥ 1 treatment-related TEAE | 3 | 4 | 5 | 5 |
| ≥ 1 Grade 3/4 TEAE | 2 | 3 | 5 | 4 |
| ≥ 1 Grade 3/4 treatment-related TEAE | 0 | 0 | 3 | 3 |
| ≥ 1 Grade ≥ 3 TEAE | 2 | 3 | 5 | 5 |
| ≥ 1 Grade ≥ 3 treatment-related TEAE | 0 | 0 | 3 | 3 |
| ≥ 1 Grade 5 TEAE | 1 | 0 | 1 | 2 |
| ≥ 1 Grade 5 treatment-related TEAE | 0 | 0 | 0 | 0 |
| ≥ 1 serious TEAE | 2 | 2 | 3 | 4 |
| ≥ 1 serious treatment-related TEAE | 0 | 0 | 0 | 2 |
| ≥ 1 TEAE leading to discontinuation of enasidenib | 0 | 0 | 0 | 3 |
| ≥ 1 treatment-related TEAE leading to discontinuation of enasidenib | 0 | 0 | 0 | 1 |
| ≥ 1 TEAE leading to dose reduction of enasidenib | 0 | 0 | 0 | 0 |
| ≥ 1 treatment-related TEAE leading to dose reduction of enasidenib | 0 | 0 | 0 | 0 |
| ≥ 1 TEAE leading to interruption of enasidenib | 0 | 2 | 3 | 5 |
| ≥ 1 treatment-related TEAE leading interruption of enasidenib | 0 | 0 | 2 | 4 |
| ≥ 1 TEAE leading to death | 1 | 0 | 1 | 2 |
| ≥ 1 treatment-related TEAE leading to death | 0 | 0 | 0 | 0 |
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.
| Participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Number of Participants With Dose-limiting Toxicities | 0 | 0 | 1 | 0 |
ECOG performance status is used by doctors and researchers to assess how a subjects disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. * 0 = Fully active (most favorable activity); * 1 = Restricted activity but ambulatory; * 2 = Ambulatory but unable to carry out work activities; * 3 = Limited self-care; * 4 = Completely disabled, no self-care (least favorable activity).
| score on a scale | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Baseline | 1.3 ± 1.15 | 0.5 ± 0.58 | 0.9 ± 0.90 | 0.9 ± 0.90 |
| Cycle 1 Day 15 | 1.7 ± 0.58 | 1.8 ± 1.50 | 0.8 ± 0.84 | 1.0 ± 0.71 |
| Cycle 2 Day 1 | 1.7 ± 0.58 | 0.8 ± 0.50 | 1.2 ± 1.30 | 0.7 ± 0.58 |
| Cycle 3 Day 1 | 1.0 | — | 1.0 ± 0.00 | 1.0 ± 0.00 |
| Cycle 4 Day 1 | 1.0 | — | 1.0 ± 0.00 | 1.0 |
| Cycle 5 Day 1 | — | — | 1.0 ± 0.00 | 1.0 |
| End of Treatment | 2.5 ± 0.71 | 0.7 ± 0.58 | 1.3 ± 1.50 | 1.7 ± 1.15 |
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.
| ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Enasidenib on Day -3 | 1403.4 ± 77.9 | 1433.0 ± 51.2 | 4540.6 ± 63.7 | 4702.9 ± 61.3 |
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.
| hours | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Enasidenib After a Single Dose on Day -3 | 2.0 (2 to 8) | 6.1 (2 to 25) | 8.0 (2 to 10) | 3.3 (2 to 24) |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After a Single Oral Dose on Day -3 | 10031.7 ± 79.0 | 11040.2 ± 55.9 | 31959.0 ± 56.7 | 29847.8 ± 59.6 |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration Time Curve From Time Zero to 72 Hours Postdose (AUC0-72) of Enasidenib After a Single Dose on Day -3 | 62420.0 ± 80.6 | 86900.7 ± 62.5 | 206214.4 ± 65.2 | 248315.9 ± 69.9 |
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.
| ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 94.2 ± 64.5 | 71.9 ± 70.8 | 273.0 ± 52.9 | 239.4 ± 64.8 |
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.
| hours | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 70.3 (8 to 74) | 71.7 (71 to 73) | 71.7 (2 to 73) | 72.0 (48 to 72) |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Metabolite AGI-16903 After a Single Dose of Enasidenib on Day -3 | 518.6 ± 64.5 | 233.3 ± 30.6 | 1358.2 ± 46.5 | 965.2 ± 67.8 |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Postdose (AUC0-72) for AGI-16903 After a Single Dose of Enasidenib on Day -3 | 7556.4 ± 42.9 | 7294.2 ± 99999 | 13752.5 ± 57.8 | 12519.5 ± 74.7 |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Enasidenib After Multiple Doses | 106522.9 ± 46.7 | 161862.9 ± 1.4 | 154248.7 ± 33.3 | 221865.0 ± 10.1 |
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.
| ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Enasidenib After Multiple Doses | 10717.9 ± 54.1 | 14945.4 ± 40.4 | 19401.1 ± 39.9 | 29316.3 ± 7.1 |
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.
| hours | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Enasidenib After Multiple Doses | 8.0 (6 to 10) | 5.9 (1 to 10) | 2.0 (1 to 2) | 2.2 (2 to 8) |
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.
| h*ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time 0 to 10 Hours Postdose (AUC0-10) for Metabolite AGI-16903 After Multiple Doses of Enasidenib | 9074.5 ± 53.6 | 13914.2 ± 13.2 | 19865.8 ± 36.8 | 23007.5 ± 34.8 |
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.
| ng/mL | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 1093.7 ± 59.5 | 1435.7 ± 29.9 | 2101.1 ± 56.7 | 2837.0 ± 31.6 |
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.
| hours | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Metabolite AGI-16903 After Multiple Doses of Enasidenib | 8.0 (2 to 10) | 5.9 (1 to 10) | 1.4 (1 to 2) | 2.2 (2 to 8) |
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.
| percentage of participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Percentage of Participants With Solid Tumors (Excluding Glioma) Who Achieved an Objective Response | 0 | 0 | 0 | 0 |
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.
| percentage of participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Percentage of Participants With Glioma Who Achieved an Objective Response | 0 | — | 0 | 0 |
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).
| percentage of participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Percentage of Participants With AITL Who Achieved an Objective Response | 0 | 0 | — | 0 |
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.
| Participants | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenb 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| QTcF Increased from Baseline ≤ 30 ms | 3 | 1 | 5 | 5 |
| QTcF Increased from Baseline > 30 to ≤ 60 ms | 0 | 3 | 0 | 0 |
| QTcF Increased from Baseline > 60 ms | 0 | 0 | 0 | 1 |
| Missing | 0 | 0 | 1 | 0 |
| no QTcF Increase from Baseline | 0 | 0 | 0 | 1 |
Collected over From first dose of study drug to 28 days after last dose; median (minimum, maximum) duration of exposure was 66 (8, 197) days across all cohorts.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Enasidenib 100 mg | 1/3 (33.3%) | 2/3 (66.7%) | 3/3 (100%) |
| Enasidenib 200 mg | 0/4 (0%) | 2/4 (50%) | 4/4 (100%) |
| Enasidenib 400 mg | 1/7 (14.3%) | 3/7 (42.9%) | 6/7 (85.7%) |
| Enasidenib 650 mg | 2/7 (28.6%) | 4/7 (57.1%) | 7/7 (100%) |
| Event | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| Disease progressionGeneral disorders | 1/3 | 0/4 | 0/7 | 0/7 |
| PneumoniaInfections and infestations | 1/3 | 0/4 | 0/7 | 0/7 |
| SepsisInfections and infestations | 1/3 | 0/4 | 0/7 | 0/7 |
| DehydrationMetabolism and nutrition disorders | 1/3 | 1/4 | 0/7 | 0/7 |
| Mental status changesPsychiatric disorders | 1/3 | 0/4 | 0/7 | 0/7 |
| Pneumonia aspirationRespiratory, thoracic and mediastinal disorders | 1/3 | 0/4 | 1/7 | 0/7 |
| Myocardial infarctionCardiac disorders | 0/3 | 1/4 | 0/7 | 0/7 |
| Sinus tachycardiaCardiac disorders | 0/3 | 1/4 | 0/7 | 1/7 |
| PyrexiaGeneral disorders | 0/3 | 1/4 | 0/7 | 0/7 |
| Septic shockInfections and infestations | 0/3 | 1/4 | 0/7 | 0/7 |
| Event | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg |
|---|---|---|---|---|
| FatigueGeneral disorders | 1/3 | 3/4 | 4/7 | 1/7 |
| NauseaGastrointestinal disorders | 1/3 | 2/4 | 5/7 | 4/7 |
| AstheniaGeneral disorders | 2/3 | 0/4 | 0/7 | 1/7 |
| Decreased appetiteMetabolism and nutrition disorders | 2/3 | 0/4 | 2/7 | 2/7 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/3 | 0/4 | 2/7 | 0/7 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 2/3 | 0/4 | 1/7 | 0/7 |
| DiarrhoeaGastrointestinal disorders | 0/3 | 0/4 | 4/7 | 3/7 |
| Blood creatinine increasedInvestigations | 0/3 | 2/4 | 1/7 | 1/7 |
| HyperkalaemiaMetabolism and nutrition disorders | 0/3 | 2/4 | 0/7 | 0/7 |
| HyponatraemiaMetabolism and nutrition disorders | 0/3 | 2/4 | 1/7 | 0/7 |
All enrolled particpants
| Age, Continuous(years) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| Mean | 56.3 ± 16.80 | 68.0 ± 5.10 | 52.0 ± 18.47 | 61.3 ± 13.34 | 58.8 ± 14.97 |
| Age, Customized(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| < 60 years | 1 | 0 | 4 | 3 | 8 |
| 60 to < 70 years | 1 | 3 | 2 | 1 | 7 |
| 70 to < 75 years | 1 | 0 | 1 | 2 | 4 |
| ≥ 75 years | 0 | 1 | 0 | 1 | 2 |
| Sex: Female, Male(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| Female | 1 | 0 | 4 | 3 | 8 |
| Male | 2 | 4 | 3 | 4 | 13 |
| Race(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| Black or African American | 1 | 0 | 0 | 0 | 1 |
| White | 2 | 4 | 6 | 4 | 16 |
| Not Reported | 0 | 0 | 1 | 3 | 4 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| 0 = Fully Active | 1 | 2 | 3 | 3 | 9 |
| 1= Restricted but Ambulatory | 0 | 2 | 2 | 2 | 6 |
| 2 = Ambulatory but Unable to Work | 2 | 0 | 2 | 2 | 6 |
| 3 = Limited Self-Care | 0 | 0 | 0 | 0 | 0 |
| 4 = Completely Disabled | 0 | 0 | 0 | 0 | 0 |
| Tumor Type(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| Cholangiocarcinoma | 0 | 0 | 1 | 3 | 4 |
| Chondrosarcoma | 1 | 1 | 1 | 0 | 3 |
| Glioma | 1 | 0 | 4 | 1 | 6 |
| Angioimmunoblastic T-cell lymphoma (AITL) | 1 | 1 | 0 | 3 | 5 |
| Other | 0 | 2 | 1 | 0 | 3 |
| Isocitrate dehydrogenase 2 (IDH2) Mutation Type(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| R172 | 3 | 3 | 3 | 6 | 15 |
| R140 | 0 | 0 | 0 | 0 | 0 |
| Other | 0 | 1 | 3 | 1 | 5 |
| Missing | 0 | 0 | 1 | 0 | 1 |
| Isocitrate dehydrogenase (IDH) 1 Gene Result(Participants) | Enasidenib 100 mg | Enasidenib 200 mg | Enasidenib 400 mg | Enasidenib 650 mg | Total |
|---|---|---|---|---|---|
| IDH1 R132 | 0 | 0 | 0 | 0 | 0 |
| Negative | 2 | 4 | 6 | 4 | 16 |
| Other | 0 | 0 | 0 | 3 | 3 |
| Missing | 1 | 0 | 1 | 0 | 2 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in Feb 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Enasidenib