Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Glasdegib Oral Tablet, Glasdegib
Glasdegib single dose · 3 trials · 5 indications
AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). An AE was considered treatment related as assigned by the investigator.
A SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or other medical events as per investigator's judgement. A SAE was considered treatment emergent if the event occurred during the on-treatment period (regardless of if it was seen prior to the start of treatment). A SAE was considered treatment related as assigned by the investigator.
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
OS is defined as the time from the date of randomization to the date of death due to any cause. Participants last known to be alive were to be censored at the date of last contact.
PK parameter of glasdegib to be calculated from the plasma concentration-time data
PK parameter of glasdegib to be calculated from the plasma concentration-time data
| Arm | Type | Description |
|---|---|---|
| Participants from B1371019 and B1371012 | EXPERIMENTAL | Azacitidine will be administered 75 mg/m2/day for 7 days every 28 days on Days 1-7 (±3 days) per local label or per the IP Manual (or SPC). Azacitidine may be administered by SC injection or IV infusion. Alternate dosing schedules to administer the 7 doses to accommodate participant and treatment center availability are allowed. The starting dose regimen will be the same as the most recent regimen received on the B1371019 or B1371012 study. Glasdegib 50, 75 or 100 mg will be orally administered daily and continuously. The starting dose regimen will be the same as the most recent regimen received on the B1371012 or B1371019 study. |
| Arm A (Intensive Study) | EXPERIMENTAL | Glasdegib + '7+3' Induction(s) |
| Arm B (Intensive Study) | PLACEBO_COMPARATOR | Placebo + '7+3' Induction(s) |
| Arm A (Non-intensive study) | EXPERIMENTAL | Glasdegib + azacitidine |
| Arm B (Non-intensive study) | PLACEBO_COMPARATOR | Placebo + azacitidine |
| Moderate Hepatic Impairment Group | EXPERIMENTAL | Subjects with Child-Pugh Classification B (score 7-9) |
| Severe Hepatic Impairment Group | EXPERIMENTAL | Subjects with Child-Pugh Classification C (score 10-15) |
| Normal Hepatic Function Group | EXPERIMENTAL | Healthy subjects with normal hepatic function |
| Name | Type | Description |
|---|---|---|
| Glasdegib | DRUG | 25 mg or 100 mg tablet |
| Azacitidine | DRUG | 100 mg/vial powder for 25 mg/mL suspension for injection |
| daunorubicin + cytarabine | DRUG | '7+3' (cytarabine 100 mg/m2, IV for 7 days by continuous infusion and daunorubicin 60 mg/m2 for 3 days). If a second induction is needed, Investigators may choose either a 5 day cytarabine continuous infusion plus daunorubicin for 2 days ('5+2') or a 7 day cytarabine continuous infusion plus daunorubicin for 3 days ('7+3'); |
| Placebo | DRUG | Matching placebo (PO) given on Day 1 and is to continue up to 2 years post randomization. Following consolidation therapy, placebo will be administered daily for up to 2 years after randomization or until they have MRD negative disease, whichever comes first. Daily placebo will continue throughout Induction(s) and Consolidation therapies regardless of dose modifications/delays in the chemotherapy. |
| cytarabine | DRUG | Consolidation with single agent cytarabine 3 g/m2 IV for adults \<60 years and 1 g/m2 for adults 60 years over 3 BID on Days 1, 3, and 5, every 28 days for up to 4 cycles or alternative single agent cytarabine consolidation schedules may be used per local prescribing information. |
| HSCT | PROCEDURE | If required, and done per standard of care post Induction(s). |
| Glasdegib 100 mg single oral dose | DRUG | A single dose of 100 mg glasdegib tablet will be administered after an overnight fast, followed by serial PK collection, discharge and follow-up. |
Inclusion Criteria: * Any participant who continues to demonstrate clinical benefit (as determined by the Principal Investigator) from study treatment with azacitidine with or without glasdegib in this Study or from Study B1371012. * Capable of giving signed informed consent as described in Appendi...
Glasdegib is an investigational small molecule being studied in acute myeloid leukemia and in hepatic impairment. It has been evaluated in Phase 3 trials in previously untreated AML, myelodysplastic syndrome, and chronic myelomonocytic leukemia, and in a Phase 1 pharmacokinetic study in patients with hepatic impairment.
Glasdegib targets SMO, a protein in the Hedgehog signaling pathway. It acts as an antagonist, meaning it blocks SMO activity. This mechanism is being investigated in oncology, specifically in acute myeloid leukemia.
Glasdegib is being developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer is the sponsor of the clinical trials evaluating Glasdegib in acute myeloid leukemia and hepatic impairment.
Glasdegib is in Phase 3 clinical development. It is investigational and has not been approved by the FDA. Two Phase 3 trials have been completed, and no active trials are currently listed.
Glasdegib has been studied in two completed Phase 3 trials: NCT03416179, which evaluated intensive chemotherapy with or without Glasdegib or azacitidine with or without Glasdegib in previously untreated AML, and NCT04842604, a continuation study in AML, MDS, or CMML. A Phase 1 hepatic impairment study, NCT03627754, is also completed.