A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)

Conditions

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome/Neoplasm
• Myelodysplastic Syndromes

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Azacitidine — DRUG
  Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for SC administration.
• ASTX030 (cedazuridine + azacitidine) — DRUG
  FDC Capsules for oral administration.
• Azacitidine — DRUG
  Powder for reconstitution to aqueous suspension for SC administration.
• ASTX030 (cedazuridine + azacitidine) — DRUG
  Tablets/Capsules for oral administration.
• Cedazuridine — DRUG
  Tablets for oral administration.
• Venetoclax — DRUG
  Oral tablets.

Study Details

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.

Key Dates

Start date

May 21, 2020

Status verified

Apr 2026

Primary completion

Nov 1, 2027

Completion

Nov 1, 2028

Study Design

Enrollment

316 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1 Monotherapy , Stage A (Dose Escalation)
  In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered.
• Experimental: Phase 1 Monotherapy, Stage B (Dose Expansion)
  In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by SC azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered. On Day 7 of Cycle 2 drug products will administered in a fed state and all other doses will be administered in fasted state.
• Experimental: Phase 2 Monotherapy, Part B, Sequence A & B
  In Sequence A: Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
• Experimental: Phase 3 Monotherapy, Sequence A & B
  In Sequence A: Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3). In Sequence B: Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles ≥3).
• Experimental: Phase 1 Combination Therapy
  Treatment Arm 1: Participants will receive oral dose of ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). Treatment Arm 2: Participants will receive SC azacitidine along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive SC azacitidine along with oral dose of venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2). At the beginning of Cycle 5, Arm 2 patients may be permitted to cross over to Arm 1.
• Experimental: Phase 2 Combination Therapy
  Participants will receive ASTX030 along with ramp-up oral dosing of venetoclax in Cycle 1 (cycle length = 28 days); participants will receive ASTX030 along with venetoclax on a specific dosing schedule in subsequent cycles (Cycles ≥2).

Primary Outcome Measure

Phase 1, 2 and 3 Monotherapy: Total Cycle Area Under the Curve (AUC) From 0 to 24 Hours (AUC0-24) Exposures [ Time Frame: Predose and at multiple timepoints post-dose up to 24 hours ]

Central Contacts

• Taiho Oncology, Inc.
  +1 844-878-2446
  [email protected]

Locations (24)

Find similar trials in Los Angeles, CA

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