Phase 1 Open-label Study of AMX-883 Alone in Participants With AML and High-risk MDS and in Combination in Participants With AML

NCT07723703 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: AMX-883-C001
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to assess the safety, pharmacokinetics, and preliminary efficacy of AMX-883 monotherapy in participants with acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS) and in combination with anticancer agents in participants with AML.

Conditions

Acute Myeloid Leukaemia; High Risk Myelodysplastic Syndrome

Keywords

Pharmacokinetics; Dose escalation; Bayesian Optimal INterval (BoIN); Bromodomain-Containing Protein 9 (BRD9); Monotherapy

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (AEs), treatment-emergent adverse events (TEAEs), adverse events of special interests (AESIs) and serious adverse events (SAEs)

  To determine the safety and tolerability of AMX-883 in participants with relapsed or refractory AML and high-risk MDS when administered as monotherapy and in combination with posaconazole.

  Until 30 days after last dose (Approximately 2 years 8 months)

• Number of participants with dose limiting toxicities (DLTs)

  To determine the maximum tolerated dose (MTD)/optimal biological dose (OBD) and the recommended dose for expansion (RDE) of AMX-883 in participants with relapsed or refractory AML and high-risk MDS when administered as monotherapy and in combination with posaconazole.

  During Cycle 1 (each cycle will be 28 days)

Secondary Outcomes (34)

• Maximum plasma concentration (Cmax)

  At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

• Minimum plasma concentration (Cmin)

  At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

• Time to Cmax (Tmax)

  At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

• Terminal plasma half-life (t½λz)

  At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

• Area under the plasma concentration-time curve from zero to infinity (AUCinf)

  At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

Study Arms (3)

Module 1 Part A (M1A): AMX-883 monotherapy dose escalation cohort

EXPERIMENTAL

Participants will receive escalating dose levels of AMX-883 administered as monotherapy.

Drug: AMX-883

Module 1 Part A (M1A): AMX-883 monotherapy food effect cohort

EXPERIMENTAL

Participants will receive a selected dose of AMX-883 from the M1A dose escalation cohort, administered as monotherapy, under fed and fasted conditions.

Drug: AMX-883

Module 1 Part B (M1B): AMX-883 + posaconazole

EXPERIMENTAL

Participants will receive a selected dose level for at least two escalating dose levels of AMX-883 selected from the M1A dose escalation cohort, administered in combination with posaconazole.

Drug: AMX-883; Drug: Posaconazole

Interventions

AMX-883 DRUG

AMX-883 will be administered orally.

Module 1 Part A (M1A): AMX-883 monotherapy dose escalation cohort; Module 1 Part A (M1A): AMX-883 monotherapy food effect cohort; Module 1 Part B (M1B): AMX-883 + posaconazole

Posaconazole DRUG

Posaconazole tablets will be administered orally.

Module 1 Part B (M1B): AMX-883 + posaconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with relapsed or refractory AML who have failed all available standard therapies or relapsed or refractory high-risk MDS with BM blasts 10-19%
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate washout from prior therapies
• Adequate kidney and liver function
• Female participants of childbearing potential must use highly effective contraception, and male participants must agree to use barrier contraception and avoid sperm donation for at least 120 days after last dose
• If enrolled in M1B: Participant must have no documented contraindication to treatment with posaconazole before start of treatment

You may not qualify if:

• Diagnosis of acute promyelocytic leukaemia or chronic myelogenous leukaemia in blast crisis
• Clinically active central nervous system (CNS) leukaemia
• Receiving immunosuppressive therapy post HSCT
• History of another malignancy that is active, progressing, or has required systemic treatment within the past 2 years
• Presence of \>Grade 1 active graft versus host disease within 4 weeks prior to C1D1
• Significant cardiovascular disease
• Family history of sudden cardiac death before 40 years of age or a family history of long QT syndrome
• Clinically significant electrolyte imbalances (e.g., hypokalaemia, hypomagnesaemia, hypocalcaemia) that may contribute to QT interval prolongation
• Clinically significant bradycardia (\<50 beats per minute) that is symptomatic or causes haemodynamic instability
• Major surgery within 4 weeks prior to C1D1 or inadequate recovery from prior surgery
• Uncontrolled intercurrent illness
• Inability to fast, swallow, ingest, or absorb oral medication due to a pre-existing condition
• History of interstitial lung disease or pneumonitis requiring systemic corticosteroid treatment
• Requirement for medications with a known risk of Torsades de Pointes that cannot be discontinued prior to study treatment
• Detectable human immunodeficiency virus (HIV) viral load

Sponsors & Collaborators

• Amphista Therapeutics Ltd: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2026
• First Posted: July 23, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 4, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share