Phase 1 Study of AUTX-703 in Relapsed/Refractory AML and MDS

A Phase 1 Study of AUTX-703 in Participants With Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes

This Phase 1, multicenter, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of AUTX-703 administered orally in subjects with advanced hematologic malignancies.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory AML; Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; Relapsed Acute Myeloid Leukemia (AML); Refractory Acute Myeloid Leukemia (AML); Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: AUTX-703

Detailed Description

This is a first-in-human, Phase 1, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of AUTX-703, an orally bioavailable lysine acetyltransferase 2A (KAT2A) and lysine acetyltransferase 2B (KAT2B) degrader, in participants with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study consists of two parts: Part A (Dose Escalation) to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and Part B (Dose Optimization) to further evaluate safety, PK, PD and efficacy at selected dosages.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University, The James Comprehensive Cancer
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • UPENN Perelman Center for Advanced Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Center for Blood Cancer at TriStar Centennia
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Participant must be ≥18 years of age

2. Participant must have confirmed diagnosis as follows:

   R/R AML and has not achieved adequate response to, cannot tolerate, or refused all approved therapies known to be active for treatment of their disease OR R/R MDS with over 10% blasts in the bone marrow and has not achieved an adequate response to at least 4 cycles of a hypomethylating agent (HMA)- containing regimen or other treatment known to be active for their disease OR R/R AML or R/R MDS that has relapsed after a hematopoietic stem cell transplant (HSCT)

3. Participant must be willing and able to comply with scheduled study visits and treatment plans.
4. Participant must be willing to undergo all study procedures unless contraindicated due to medical risk.
5. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2
6. Participant must have adequate hepatic function
7. Participant must have adequate renal function
8. Participant must have adequate cardiovascular function
9. Participant must have a white blood cell (WBC) count ≤20 × 10⁹/L (with stable hydroxyurea use allowed)
10. Participant must meet timing requirements with respect to prior therapy and surgery
11. Participant must agree to use effective contraception during the study and for the required post-treatment period: Males: Use condoms (even if vasectomized) during the study and for 90 days post-treatment. Females of childbearing potential: Use a combination of 1 highly effective and 1 effective method of contraception during the study and for 180 days post-treatment.

Key Exclusion Criteria:

1. Participant is unable to provide informed consent and/or to follow protocol requirements.
2. Participant has undergone chimeric antigen receptor T cell therapy or HSCT within 60 days of the first dose of study treatment or has active clinically significant graft-versus-host disease (GVHD)
3. Participant has another malignancy that may interfere with diagnosis and treatment of R/R AML or R/R MDS.
4. Participant has an active severe infection that requires anti-infective therapy or has an unexplained temperature of >38.5°C during screening visits or on their first day of study treatment.
5. Participant has a known sensitivity to AUTX-703 or any of its components.
6. Participant is taking systemic strong CYP3A4 inhibitors or inducers within 14 days of the first dose of study treatment.
7. Participant who are taking proton pump inhibitors should be switched to another acid-reducing agent such as an antacid or H2 blocker
8. Participant is taking P-gp and breast cancer resistance protein (BCRP) inhibitors or inducers within 14 days of first dose of study treatment.
9. Participant has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections with detectable viral load
10. Participant has experienced AIDS related illness within the past 6 months or have detectable HIV viral load.
11. Participant has an uncontrolled intercurrent illness
12. Participant has active Class III or IV cardiovascular disease within 6 months prior to the start of study treatment
13. Participant is unable to tolerate the administration of oral medication or has GI dysfunction that would preclude adequate absorption, distribution, metabolism, or excretion of an oral medication
14. Participant is pregnant or breastfeeding or is planning to become pregnant within 1 year of the start of study treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation - Part A; Participants will receive escalating dosages of AUTX-703 orally in tablet form once, twice or three times weekly to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).	Drug: AUTX-703; AUTX-703 administered orally
Experimental: Dose Optimization - Part B, Dosage 1; Participants will receive AUTX-703 at the first selected dosage determined from Part A, administered orally in tablet form either once, twice or three times weekly to further evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity at this specified dose.	Drug: AUTX-703; AUTX-703 administered orally
Experimental: Dose Optimization - Part B, Dosage 2; Participants will receive AUTX-703 at the second selected dosage determined from Part A, administered orally in tablet form either once, twice or three times weekly to further evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity at this specified dose.	Drug: AUTX-703; AUTX-703 administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs), Dose-Limiting Toxicities (DLTs), and Serious Adverse Events (SAEs)	To assess the safety and tolerability of AUTX-703 by evaluating the incidence and severity of AEs, DLTs, SAEs, and AEs leading to treatment discontinuation.	From the first dose through 28 days after the last dose of study drug.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)		Up to 24 months
AML: Complete remission (CR) rate		Up to 18 months
To Identify the Recommended Phase 2 Dose (RP2D) of AUTX-703	To determine the RP2D of AUTX-703 based on safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity data.	From the first dose through 28 days after the last dose of study drug.
Peak Plasma Concentration (Cmax)		From the first dose through the first treatment cycle (28 days)
Time to Maximum Concentration (Tmax)		From the first dose through the first treatment cycle (28 days)
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUCinf)		From the first dose through the first treatment cycle (28 days)
Area Under the Plasma Concentration-Time Curve to the Last Measurable Concentration (AUClast)		From the first dose through the first treatment cycle (28 days)
Elimination Half-Life (t½)		From the first dose through the first treatment cycle (28 days)
Apparent Clearance (CL/F)		From the first dose through the first treatment cycle (28 days)
Apparent Volume of Distribution (Vd/F)		From the first dose through the first treatment cycle (28 days)
To characterize the PD of AUTX-703	To evaluate changes in KAT2A and KAT2B levels in peripheral blood and bone marrow as markers of pharmacodynamic response	From the first dose through 28 days after the last dose of study drug
AML: CR + CRh rate		Up to 18 months
AML: Duration of CR		Up to 18 months
AML: Duration of CR + CRh		Up to 18 months
AML: Duration of response (DOR)		Up to 18 months
AML: Transfusion independence (TI) rate		Up to 18 months
AML: Event free survival (EFS)		Up to 24 months
AML: Overall survival (OS)		Up to 24 months
MDS: Complete remission (CR) rate		Up to 18 months
MDS: PR rate		Up to 18 months
MDS: CR+PR rate		Up to 18 months
MDS: Duration of CR		Up to 18 months
MDS: Duration of PR		Up to 18 months
MDS: Duration of CR+PR		Up to 18 months
MDS: Event free survival (EFS)		Up to 24 months
MDS: Overall survival (OS)		Up to 24 months

Collaborators and Investigators

• Sponsor: Auron Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Relapsed/Refractory AML; Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; AUTX-703; KAT2A/B degrader
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
• Other Study ID Numbers: AUTX-703-001

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.: No