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

A Phase 1, Open-Label, Multi-Centre Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of AMX-883 Monotherapy in Participants With Acute Myeloid Leukaemia and High-Risk Myelodysplastic Syndrome and in Combination With Anticancer Agents in Participants With Acute Myeloid Leukaemia

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.

Study Overview

• Status: Not yet recruiting
• Conditions: High Risk Myelodysplastic Syndrome; Acute Myeloid Leukaemia
• Intervention / Treatment: Drug: AMX-883; Drug: Posaconazole

Detailed Description

This is a modular, Phase 1, open-label, multi-centre dose-escalation study investigating AMX-883 in participants with relapsed/refractory AML and high-risk MDS. The study comprises Module 1, which will evaluate AMX-883 as monotherapy and in combination with posaconazole.

Module 1 consists of three parts:

• Part A consists of the monotherapy dose escalation cohorts and investigation of the food-effect at selected dose(s).
• Part B consists of AMX-883 in combination with posaconazole dose escalation cohorts.

Other modules may be added by protocol amendment. The study aims to establish optimal dosing and preliminary efficacy data to support further clinical development of AMX-883.

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Known serologic status reflecting active hepatitis B or C infection
• Active uncontrolled systemic fungal, bacterial, viral, or other infection or a condition predisposing to severe infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1 Part A (M1A): AMX-883 monotherapy dose escalation cohort; Participants will receive escalating dose levels of AMX-883 administered as monotherapy.	Drug: AMX-883; AMX-883 will be administered orally.
Experimental: Module 1 Part A (M1A): AMX-883 monotherapy food effect cohort; 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; AMX-883 will be administered orally.
Experimental: Module 1 Part B (M1B): AMX-883 + posaconazole; 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; AMX-883 will be administered orally.; Drug: Posaconazole; Posaconazole tablets will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax)	To characterise the PK (Cmax) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Cmax) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Minimum plasma concentration (Cmin)	To characterise the PK (Cmin) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Cmin) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Time to Cmax (Tmax)	To characterise the PK (Tmax) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Tmax) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Terminal plasma half-life (t½λz)	To characterise the PK (t½λz) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (t½λz) of AMX-883.	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)	To characterise the PK (AUCinf) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (AUCinf) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Oral plasma clearance (CL/F)	To characterise the PK (CL/F) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (CL/F) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Oral volume of distribution during terminal phase (Vz/F)	To characterise the PK (Vz/F) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (Vz/F) of AMX-883.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Mean residence time (MRT)	To characterise the PK (MRT) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (MRT) of AMX-883.	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 tau (AUC0-tau) where tau=12	To characterise the PK (AUC0-tau) parameters of AMX-883 after a single dose and at steady state when administered as monotherapy and in combination with posaconazole and to characterise the effect of a high-fat meal on the PK (AUC0-tau) of AMX-883. AUC at other timepoints may also be derived.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)
Composite complete remission (CRc) (AML)	CRc is defined as percentage of participants with Complete remission (CR) and complete remission with partial haematologic recovery (CRh) and complete remission with incomplete count recovery (CRi). This will be used to explore early evidence of antileukaemic activity (ALA) of AMX-883 when administered as monotherapy and in combination with posaconazole in participants.	Approximately 2 years 8 months
Morphologic leukaemia-free state (MLFS) (AML)	MLFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Overall Response rate (ORR) (AML)	ORR is defined as CR, CRh, or CRi with or without MRD. ORR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Duration of remission (DOR) (AML)	DOR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Transfusion independence (TI) (AML)	TI will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Relapse-free survival (RFS) (AML)	RFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Progression-free survival (PFS) (AML)	PFS is defined as the time from the first dose until which participants can continue receiving treatment without experience any progressive disease. PFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Event-free survival (EFS) (AML)	EFS is defined as the failure to achieve CR. EFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Time to response (TTR) (AML)	TTR is defined as the time taken to achieve CR, ORR and CRc after starting the treatment. TTR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Overall survival (OS) (AML)	OS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
Treatment failure (AML)	Treatment failure will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
30-day and 60-day mortality rate (Extramedullary Disease- 30 [ED-30] and ED-60) (AML)	ED-30 and ED-60 will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with AML.	Approximately 2 years 8 months
CR (high-risk MDS)	CR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
CR equivalent (high-risk MDS)	CR equivalent will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
Partial remission (PR) (high-risk MDS)	PR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
Complete remission with limited count recovery (CRL) (high-risk MDS)	CRL will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
CRh (high-risk MDS)	CRh will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
Haematologic improvement (HI) (high-risk MDS)	HI will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
ORR (high-risk MDS)	ORR is defined by CR (or CR equivalent) + PR + CRL + CRh + HI. ORR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
DOR (high-risk MDS)	DOR is defined as CR (or CR equivalent) + PR + CRL + CRh + HI. DOR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
TTR (high-risk MDS)	TTR is defined as the time from first dose of study treatment to the first documented evidence of achieving a CR, ORR and CRc. TTR will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
PFS (high-risk MDS)	PFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
EFS (high-risk MDS)	EFS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
OS (high-risk MDS)	OS will be used to explore early evidence of ALA of AMX-883 when administered as monotherapy and in combination with posaconazole in participants with high-risk MDS.	Approximately 2 years 8 months
Change from baseline in BRD9 expression levels in peripheral blood mononuclear cells (PBMCs)	To investigate biomarkers potentially related to AMX-883 activity when administered as monotherapy and in combination with posaconazole.	At predefined intervals from Cycle 1 Day 1 (C1D1) until completion of treatment period (Approximately 2 years 8 months)

Collaborators and Investigators

• Sponsor: Amphista Therapeutics Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 4, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: July 20, 2026
• First Submitted That Met QC Criteria: July 20, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 20, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Dose escalation; Monotherapy; Bayesian Optimal INterval (BoIN); Bromodomain-Containing Protein 9 (BRD9)
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; posaconazole
• Other Study ID Numbers: AMX-883-C001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD information will not be shared due to legal/proprietary restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes