Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Enasidenib · 7 trials · 11 indications
Hematologic response to enasidenib will be evaluated according to a modified version of the IWG 2006 Criteria for Hematologic Improvement for patients with MDS on clinical trials
Estimation of maximum observed plasma concentration
Estimation of AUC from time zero extrapolated to infinity
Estimation of AUC from time zero extrapolated to last time point
Time to reach Cmax
Observed maximum concentration
Area under the concentration-time curve calculated from time zero to infinity
Area under the concentration-time curve calculated from time zero to the last measured time point
Time to Cmax
Terminal elimination half-life
Apparent clearance of drug from plasma after extravascular administration
Apparent volume of distribution during the terminal phase
Area under the probe plasma concentration-time curve calculated from time zero to 30 hours
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.
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.
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).
Toxicity severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT was defined as: • Non-hematologic toxicities: CTCAE ≥ Grade 3 with the exception of ≥ Grade 3 blood bilirubin increases in participants with a uridine diphosphate- glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) mutation. In participants with a UGT1A1 mutation, blood bilirubin increases of \> 5× upper limit of normal (ULN) were considered a DLT. • Hematologic toxicities: Prolonged myelosuppression, defined as persistence of ≥ Grade 3 neutropenia or thrombocytopenia (by NCI CTCAE v4.03), leukemia-specific criteria, i.e., marrow cellularity \<5% on Day 28 or later from the start of study drug without evidence of leukemia) at least 42 days after the initiation of Cycle 1 therapy. Leukemia-specific grading was used for cytopenias (based on percentage decrease from Baseline: 50 to 75% = Grade 3, \>75% = Grade 4)
A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Requires inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: • Resulted in death; • Was life threatening; • Required inpatient hospitalization or prolongation of existing hospitalization; • Resulted in persistent or significant disability/incapacity; • Was a congenital anomaly/birth defect; • Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
ORR is defined as the percentage of participants achieving an overall response of complete response (CR), CR with incomplete neutrophil recovery (CRi), CR with incomplete platelet recovery (CRp), partial response (PR), or morphologic leukemia-free state (MLFS) based on the 2003 revised International Working Group (IWG) criteria for AML, assessed by the Investigator. CR: • Absolute neutrophil count (ANC) \> 1.0 x10⁹/L • Platelet count \> 100 x10⁹/L • Bone marrow (BM) blasts \< 5% • Absence of blasts with Auer rods • Independence of red cell transfusions CRi: • All CR criteria except for residual neutropenia (ANC \< 1.0 x 10⁹/L CRp: • All CR criteria except for residual thrombocytopenia (platelets \< 100 x 10⁹/L) PR: • Meets hematologic criteria of CR • Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%. MLFS: • Bone marrow blasts \< 5% • Absence of blasts with Auer rods • Absence of extramedullary disease • No hematologic recovery required
A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
A TEAE is any adverse event that began or worsened on or after the start of investigational product (IP) through 28 days after the last dose. A treatment-related TEAE is a TEAE that is suspected (possibly or probably related) by the Investigator to be related to the IP. A serious AE is one that at any dose of IP or at any time during the observation period met the following criteria: - Resulted in death; - Was life threatening; - Required inpatient hospitalization or prolongation of existing hospitalization; - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Was medically important. The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 4.03, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
| Arm | Type | Description |
|---|---|---|
| Enasidenib | EXPERIMENTAL | Participants will receive enasidenib 100 mg daily for 18 cycles (each cycle is 28 days). Participants will continue treatment with enasidenib until confirmed progression to AML or MDS, development of unacceptable toxicity, or suspicion of disease progression, provided the patient is deriving clinical benefit, which will be determined at the discretion of the principal investigator. |
| Enasidenib (CC-90007) tablet | EXPERIMENTAL | Participants will receive one 100 mg enasidenib (CC-90007) tablet the morning of Day 1 which will be administered in the fasted state. |
| Treatment A: Administration of enasidenib fasted | EXPERIMENTAL | A single oral 100 mg dose of enasidenib reference formulation will be given under fasted condition. |
| Treatment B: Administration of enasidenib fasted | EXPERIMENTAL | A single oral 100 mg dose of enasidenib test formulation will be given under fasted condition. |
| Treatment C: Administration of ensidenib fed | EXPERIMENTAL | A single oral 100 mg dose of enasidenib test formulation will be given under fed condition. |
| Arm 1: Administration of enasidenib and Arm 1 probes | EXPERIMENTAL | Part 1: Subjects will receive prescribed doses of Arm 1 probes on Day -1, followed by the first enasidenib dose on Day 1. Subjects will continue to take enasidenib once daily for 27 more days. On Day 28, subjects will receive the Arm 1 probes again together with the Day 28 dose of enasidenib. Part 2: the subjects continue to receive daily doses of enasidenib for the next 28 days (equivalent to a cycle). The subject will continue in subsequent cycles until the end of the study (28 months) or termination |
| Arm 2: Administration of enasidenib and Arm 2 probes | EXPERIMENTAL | Part 1: Subjects will receive prescribed doses of Arm 2 probes on Day -1, followed by the first enasidenib dose on Day 1. Subjects will continue to take enasidenib once daily for 27 more days. On Day 28, subjects will receive the Arm 2 probes again together with the Day 28 dose of enasidenib. Part 2: the subjects continue to receive daily doses of enasidenib for the next 28 days (equivalent to a cycle). The subject will continue in subsequent cycles until the end of the study (28 months) or termination |
| Arm 3: Administration of Enasidenib and Arm 3 probes | EXPERIMENTAL | Part 1: Subjects will receive prescribed doses of Arm 3 probes on Day -1, followed by the first enasidenib dose on Day 1. Subjects will continue to take enasidenib once daily for 27 more days. On Day 28, subjects will receive the Arm 3 probes again together with the Day 28 dose of enasidenib. Part 2: the subjects continue to receive daily doses of enasidenib for the next 28 days (equivalent to a cycle). The subject will continue in subsequent cycles until the end of the study (28 months) or termination. |
| Name | Type | Description |
|---|---|---|
| Enasidenib | DRUG | Provided by BMS. |
| Arm 1 probes | DRUG | caffeine, dextromethorphan, flurbiprofen, midazolam, and omeprazole |
| Arm 2 Probes | DRUG | digoxin and rosuvastatin |
| Arm 3 probes | DRUG | pioglitazone |
Inclusion Criteria: * Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds: * Hgb \<10 g/dL * ANC \<1.8 × 109/L * Platelets \<100 × 109/L * IDH2 gene mutation (R140 or R172), performed locally, at a frequen...
Enasidenib is an investigational small molecule being studied for use in acute myeloid leukemia, hematologic neoplasms, clonal cytopenia of undetermined significance, solid tumors, and hepatic impairment. It is also studied in healthy volunteers for pharmacokinetic assessments. The drug is in clinical development and is not approved.
Enasidenib targets the IDH2 mutation, as it is being studied in patients with IDH2-mutant advanced solid tumors and hematologic malignancies. The drug is a small molecule kinase inhibitor, classified under the -nib (kinase) target class.
Enasidenib is developed by Bristol-Myers Squibb Company, traded on the New York Stock Exchange under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various patient populations.
Enasidenib is in Phase 2 clinical development. The drug is investigational and has not been approved by regulatory authorities. It is being studied in multiple Phase 1 trials, with one active Phase 2 trial ongoing.
Enasidenib has been studied in several clinical trials, including NCT02273739 for advanced solid tumors with IDH2 mutations, NCT03290443 and NCT04573582 for hepatic impairment, and NCT04310527 for bioavailability in healthy volunteers. These trials are completed.
Enasidenib is also known as AG-221 and CC-90007. Clinical trial records refer to the drug by these alternative names, which are used interchangeably in research documentation.