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

Phase 1

Recruiting

• Conditions: Relapsed Acute Myeloid Leukemia (AML); Refractory Acute Myeloid Leukemia (AML); Relapsed/Refractory AML; Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
• Interventions: Drug: AUTX-703

• Registration Number: NCT06846606
• Lead Sponsor: Auron Therapeutics, Inc.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2025-02-06
• Study First Submitted QC: 2025-02-20
• Study First Posted: 2025-02-26
• Status Verified: 2025-04
• Study Start: 2025-05-01
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2027-04
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 69

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation - Part A	AUTX-703	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).
Dose Optimization - Part B, Dosage 1	AUTX-703	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.
Dose Optimization - Part B, Dosage 2	AUTX-703	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events (AEs), Dose-Limiting Toxicities (DLTs), and Serious Adverse Events (SAEs)	From the first dose through 28 days after the last dose of study drug.	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.

Secondary Outcome Measures

Name	Time	Method
To Identify the Recommended Phase 2 Dose (RP2D) of AUTX-703	From the first dose through 28 days after the last dose of study drug.	To determine the RP2D of AUTX-703 based on safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity data.
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	From the first dose through 28 days after the last dose of study drug	To evaluate changes in KAT2A and KAT2B levels in peripheral blood and bone marrow as markers of pharmacodynamic response
AML: Complete remission (CR) rate	Up to 18 months
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
Objective response rate (ORR)	Up to 24 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

Trial Locations

Locations (9)

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

H Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Ohio State University, The James Comprehensive Cancer; 🇺🇸 Columbus, Ohio, United States

UPENN Perelman Center for Advanced Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Center for Blood Cancer at TriStar Centennia; 🇺🇸 Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States