Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication IDHIFA is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test ( 1.1 ). FDA label
Also known as AG-221, AG-221 mesylate, AGI-12910, AGI-12910 mesylate, CC-90007, IDHIFA
Enasidenib · 7 trials · 12 indications
The time between randomization and death from any cause. Participants who drop-out or are alive at the end of trial will have their OS times censored at the time of last contact, as appropriate.
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
Area under the probe plasma concentration-time curve calculated from time zero to 30 hours
Observed maximum probe 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
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 |
|---|---|---|
| AG-221 plus Best supportive care (BSC) | EXPERIMENTAL | Continuous 28-day cycles of AG 221 100 mg orally (PO) once a day (QD) for 28 days, plus BSC. |
| Conventional care regimen (CCR) | ACTIVE_COMPARATOR | Continuous 28-day cycles of BSC only, azacitidine subcutaneously (SC) plus BSC, low-dose cytarabine (LDAC) SC plus BSC, or intermediate-dose cytarabine (IDAC) intravenously (IV) plus BSC. Subjects will be assigned by the investigator to one of the CCR treatment options based on the investigator's assessment of subjects' eligibility. |
| 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. |
| 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 |
|---|---|---|
| AG-221 | DRUG | Continuous 28-day cycles of AG 221 100 mg orally (PO) once a day (QD) for 28 days |
| BSC | OTHER | Best supportive care includes, hydroxyurea for leukocytosis and/or differentiation-like syndrome, anti-infectives, analgesics, antiemetics, antipyretics, transfusions and nutritional support |
| Azacitidine | DRUG | continuous 28-day cycles of azacitidine 75 mg/m2/day SC for 7 days, plus BSC |
| Low-dose cytarabine (LDAC) | DRUG | continuous 28-day cycles of cytarabine 20 mg SC twice a day (BID) for 10 days, plus BSC |
| Intermediate-dose cytarabine (IDAC) | DRUG | 28-day cycles of cytarabine 0.5 to 1.5 g/m2/day IV for 3 to 6 days, per standard institutional practice, plus BSC; only BSC given after IDAC therapy concludes per standard institutional practice |
| 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: Subjects must satisfy the following criteria to be enrolled in the study: 1. Subject is ≥ 60 years of age at the time of signing the ICF 2. Subject has primary (ie, de novo) or secondary (progression of MDS or myeloproliferative neoplasms (\[MPN\], or therapy-related) AML accor...
Enasidenib is a small molecule IDH2 inhibitor developed by Bristol-Myers Squibb Company (ticker BMY). It is being studied in hematology, including clonal cytopenia of undetermined significance, acute myeloid leukemia, other myeloid neoplasms, hepatic impairment, and solid tumors. It is also known by the code name AG-221 and CC-90007.
Enasidenib is being evaluated in clonal cytopenia of undetermined significance (CCUS) in patients whose disease carries IDH2 mutations. The recruiting Phase 2 trial NCT06240754 is a decentralized study enrolling adults 18 years and older in the United States, with a planned enrollment of 15 participants. Enasidenib is investigational for this indication.
Enasidenib targets IDH2, the isocitrate dehydrogenase 2 enzyme, and acts as an inhibitor of that target. Its development is biomarker selected, meaning trials enroll patients whose tumors or blood disorders carry IDH2 mutations. This targeted mechanism underlies its study across myeloid malignancies and related hematologic conditions.
Enasidenib is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY. The compound is also referenced in company and trial documents by the code names AG-221 and CC-90007.
Enasidenib is in Phase 2 development for clonal cytopenia of undetermined significance, with earlier Phase 1 pharmacokinetic and drug interaction studies also conducted. It remains an investigational agent in clinical development and is not described here as approved for any indication.
Enasidenib trials include NCT06240754, a recruiting Phase 2 decentralized study in clonal cytopenia of undetermined significance, and NCT04573582, a completed Phase 1 pharmacokinetic study in hepatic impairment. Completed Phase 1 studies NCT03720366 and NCT03290443 examined drug interactions in acute myeloid leukemia and pharmacokinetics in moderate to severe hepatic impairment, respectively.
Yes. Enasidenib is also known as AG-221, and it has additionally been referenced by the code CC-90007. These names identify the same small molecule IDH2 inhibitor developed by Bristol-Myers Squibb Company, so search results and trial records using AG-221 or CC-90007 refer to enasidenib.