Study ASTX030-01 is a multi-phase study comprising of Phases 1-3 Monotherapy arms, and Phase 1 and Phase 2 Combination Therapy arms. Phase 1 Monotherapy consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 Monotherapy is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 Monotherapy is a randomized open-label crossover study comparing the final fixed dose of oral ASTX030 to SC azacitidine. Phase 1 Combination Therapy is an open-label, multicenter, randomized, exploratory study comparing ASTX030 and SC azacitidine in combination with venetoclax in participants with treatment-naïve AML. Phase 2 Combination Therapy is an open-label, single arm, study evaluating the efficacy, safety, pharmacokinetics (PK), and drug interactions of ASTX030 in combination with venetoclax in participants with treatment-naïve AML.
The duration of this multi-phase study is approximately 8 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Participants with adequate organ function.
For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
Participants with no major surgery within 3 weeks before first study treatment.
Has an active uncontrolled gastric or duodenal ulcer.
Has poor medical risk because of other conditions.
Has known human immunodeficiency virus (HIV) infection.
Is known to be positive for Hepatitis B or C infection.
Crossover
Azacitidine
DrugTablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.
ASTX030 (cedazuridine + azacitidine)
DrugFDC Capsules for oral administration.
Azacitidine
DrugPowder for reconstitution to aqueous suspension for SC administration.
ASTX030 (cedazuridine + azacitidine)
DrugTablets/Capsules for oral administration.
Cedazuridine
DrugTablets for oral administration.
Venetoclax
DrugOral tablets.
6
Treatment groupsSee each treatment group below.
Phase 1, 2 and 3 Monotherapy: Total Cycle Area Under the Curve (AUC) From 0 to 24 Hours (AUC0-24) Exposures
Ratio of azacitidine total cycle AUC0-24 exposures after oral ASTX030 over SC azacitidine.
Phase 1 Combination Therapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Phase 1 and 2 Combination Therapy: Complete Response (CR) Rate as Assessed by the Investigator
Phase 1 Combination Therapy: AUC0-24 of Venetoclax With ASTX030
Phase 1, 2 and 3 Monotherapy: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Phase 1, 2 and 3 Monotherapy: Change in Deoxyribonucleic Acid (DNA) Methylation
Percent long interspersed nuclear elements 1 (LINE-1) methylation change (demethylation) from baseline in Cycle 1 (Phase 1) and compared between SC azacitidine and ASTX030 in Cycles 1 and 2 (Phase 2 and 3).
Phase 1, 2 and 3 Monotherapy: Best CR Rate in Participants with MDS, CMML, or MDS/Myeloproliferative Neoplasms (MPN)
Phase 1, 2 and 3 Monotherapy: AML-free Survival for Participants with MDS, CMML, or MDS/MPN
Number of days from the date of randomization (date of first treatment in Phase 1) to either the date of MDS, CMML, or MDS/MPN progression to AML or the date of death from any cause
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