Clinical trial NCT06846606: Phase 1 Study of AUTX-703 in Relapsed/Refractory AML and MDS
Official title: A Phase 1 Study of AUTX-703 in Participants With Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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)
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
Lead sponsor: Auron Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs), Dose-Limiting Toxicities (DLTs), and Serious Adverse Events (SAEs)
timeFrame: From the first dose through 28 days after the last dose of study drug.
Secondary outcomes:
measure: To Identify the Recommended Phase 2 Dose (RP2D) of AUTX-703
timeFrame: From the first dose through 28 days after the last dose of study drug.
measure: Peak Plasma Concentration (Cmax)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Time to Maximum Concentration (Tmax)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Area Under the Plasma Concentration-Time Curve from Time Zero to Infinity (AUCinf)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Area Under the Plasma Concentration-Time Curve to the Last Measurable Concentration (AUClast)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Elimination Half-Life (t½)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Apparent Clearance (CL/F)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: From the first dose through the first treatment cycle (28 days)
measure: To characterize the PD of AUTX-703
timeFrame: From the first dose through 28 days after the last dose of study drug
measure: AML: Complete remission (CR) rate
timeFrame: Up to 18 months
measure: AML: CR + CRh rate
timeFrame: Up to 18 months
measure: AML: Duration of CR
timeFrame: Up to 18 months
measure: AML: Duration of CR + CRh
timeFrame: Up to 18 months
measure: Objective response rate (ORR)
timeFrame: Up to 24 months
measure: AML: Duration of response (DOR)
timeFrame: Up to 18 months
measure: AML: Transfusion independence (TI) rate
timeFrame: Up to 18 months
measure: AML: Event free survival (EFS)
timeFrame: Up to 24 months
measure: AML: Overall survival (OS)
timeFrame: Up to 24 months
measure: MDS: Complete remission (CR) rate
timeFrame: Up to 18 months
measure: MDS: PR rate
timeFrame: Up to 18 months
measure: MDS: CR+PR rate
timeFrame: Up to 18 months
measure: MDS: Duration of CR
timeFrame: Up to 18 months
measure: MDS: Duration of PR
timeFrame: Up to 18 months
measure: MDS: Duration of CR+PR
timeFrame: Up to 18 months
measure: MDS: Event free survival (EFS)
timeFrame: Up to 24 months
measure: MDS: Overall survival (OS)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University, The James Comprehensive Cancer
state: Ohio
city: Philadelphia
country: United States
facility: UPENN Perelman Center for Advanced Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Center for Blood Cancer at TriStar Centennia
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: