A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML

Taiho Pharma

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Myelodysplastic Syndrome/Neoplasm; Myelodysplastic Syndromes; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Treatments: Drug: ASTX030 (cedazuridine + azacitidine); Drug: Azacitidine; Drug: Cedazuridine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04256317

ASTX030-01

Details and patient eligibility

About

Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 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 is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of this phase 1-3 study is approximately 7 years.

Full description

The Phase 1 and Phase 2 arms have completed enrollment. The Phase 3 arm is open for enrollment.

Enrollment: 235 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Phase 2:

1. Has Confirmed MDS, CMML, MDS/MPN or AML diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice.

Phase 3:

1. Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice:

   a) French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

3. Participants with adequate organ function.

4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).

5. Participants with no major surgery within 3 weeks before first study treatment.

6. Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.

7. Participants with projected life expectancy of at least 12 weeks.

Exclusion criteria

Phase 2 and 3:

1. Has an active uncontrolled gastric or duodenal ulcer.
2. Has poor medical risk because of other conditions.
3. Has known human immunodeficiency virus (HIV) infection.
4. Is known to be positive for Hepatitis B or C infection.
5. Has a life-threatening illness.
6. Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
7. Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
8. Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
9. Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
10. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

235 participants in 4 patient groups

Phase 1, Stage A (Dose Escalation)

Experimental group

Description:

In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered.

Treatment:

Drug: Cedazuridine

Drug: Azacitidine

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: Azacitidine

Phase 1, Stage B (Dose Expansion)

Experimental group

Description:

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.

Treatment:

Drug: Cedazuridine

Drug: Azacitidine

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: Azacitidine

Phase 2, Part B, Sequence A & B

Experimental group

Description:

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).

Treatment:

Drug: Azacitidine

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: Azacitidine

Phase 3, Sequence A & B

Experimental group

Description:

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).

Treatment:

Drug: Azacitidine

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: ASTX030 (cedazuridine + azacitidine)

Drug: Azacitidine