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

NCT06846606 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: AUTX-703-001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 9

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.

Conditions

Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML); Relapsed Acute Myeloid Leukemia (AML); Refractory Acute Myeloid Leukemia (AML); Relapsed/Refractory AML

Keywords

AUTX-703; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Relapsed/Refractory AML; Acute Myeloid Leukemia; Relapsed Myelodysplastic Syndromes; Refractory Myelodysplastic Syndromes; KAT2A/B degrader; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (26)

• 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.

• 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)

Study Arms (3)

Dose Escalation - Part A

EXPERIMENTAL

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

Dose Optimization - Part B, Dosage 1

EXPERIMENTAL

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

Dose Optimization - Part B, Dosage 2

EXPERIMENTAL

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

Interventions

AUTX-703 DRUG

AUTX-703 administered orally

Dose Escalation - Part A; Dose Optimization - Part B, Dosage 1; Dose Optimization - Part B, Dosage 2

Eligibility Criteria

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

You may qualify if:

• Participant must be ≥18 years of age
• 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)
• Participant must be willing and able to comply with scheduled study visits and treatment plans.
• Participant must be willing to undergo all study procedures unless contraindicated due to medical risk.
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2
• Participant must have adequate hepatic function
• Participant must have adequate renal function
• Participant must have adequate cardiovascular function
• Participant must have a white blood cell (WBC) count ≤20 × 10⁹/L (with stable hydroxyurea use allowed)
• Participant must meet timing requirements with respect to prior therapy and surgery
• 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.

You may not qualify if:

• Participant is unable to provide informed consent and/or to follow protocol requirements.
• 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)
• Participant has another malignancy that may interfere with diagnosis and treatment of R/R AML or R/R MDS.
• 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.
• Participant has a known sensitivity to AUTX-703 or any of its components.
• Participant is taking systemic strong CYP3A4 inhibitors or inducers within 14 days of the first dose of study treatment.
• Participant who are taking proton pump inhibitors should be switched to another acid-reducing agent such as an antacid or H2 blocker
• Participant is taking P-gp and breast cancer resistance protein (BCRP) inhibitors or inducers within 14 days of first dose of study treatment.
• Participant has active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections with detectable viral load
• Participant has experienced AIDS related illness within the past 6 months or have detectable HIV viral load.
• Participant has an uncontrolled intercurrent illness
• Participant has active Class III or IV cardiovascular disease within 6 months prior to the start of study treatment
• 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
• Participant is pregnant or breastfeeding or is planning to become pregnant within 1 year of the start of study treatment

Sponsors & Collaborators

• Auron Therapeutics, Inc.: lead

Study Sites (9)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Ohio State University, The James Comprehensive Cancer

Columbus, Ohio, 43210, United States

Location

UPENN Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Center for Blood Cancer at TriStar Centennia

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Model Details: This study consists of two parts: Part A (Dose Escalation) and Part B (Dose Optimization). In Part A, participants are assigned sequentially to escalating dosages of AUTX-703 to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D). In Part B, participants are randomly assigned to receive one of two dosages of AUTX-703 for safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity.

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 26, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-03

Locations

US (9)