Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia.
In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.
Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
Arm C: Participants receiving revumenib in combination with cobicistat.
Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor).
Diagnosis of active acute promyelocytic leukemia.
Isolated extramedullary relapse (Phase 2 Cohorts 2A-2C only).
Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
Sequential
revumenib
Drugrevumenib orally
cobicistat
DrugPhase 1 Arm C participants will receive 150 mg cobicistat daily.
Number of participants with dose-limiting toxicities (DLTs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Number of participants with treatment-emergent adverse events (TEAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Cmax (Phase 1)
Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)
Tmax (Phase 1)
Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)
Transfusion independence (Phase 2 [Cohorts 2A-2C])
Transfusion independence is defined as any transfusion-free period lasting for at least 56 consecutive days
CRc rate (Phase 2 [Cohorts 2A-2C])
To assess the composite definition of complete remission (CRc) rate (Phase 2 \[Cohorts 2A-2C\])
ORR (CRc+ morphological leukemia-free state [MLFS] + partial remission [PR]) (Phase 2 [Cohorts 2A-2C])
To assess the overall response rate (ORR) of revumenib (Phase 2 \[Cohorts 2A-2C\])
TTR (Phase 2 [Cohorts 2A-2C])
To assess the time to response (TTR) of revumenib (Phase 2 \[Cohorts 2A-2C\])
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