AUTX-703 for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 8 trial locations

Overseen By Auron Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Auron Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, P-gp inhibitors

Disqualifiers: Active infection, Other malignancy, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new oral treatment called AUTX-703 for individuals with certain blood cancers. It specifically targets those with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who have not responded well to previous treatments. The study explores different doses to determine the optimal one while monitoring for side effects. Suitable candidates have AML or MDS that has not improved with other therapies or have relapsed after a stem cell transplant. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong CYP3A4 inhibitors or inducers, and P-gp and BCRP inhibitors or inducers, at least 14 days before starting the study treatment. If you are taking proton pump inhibitors, you should switch to another acid-reducing agent like an antacid or H2 blocker.

Is there any evidence suggesting that AUTX-703 is likely to be safe for humans?

Research shows that AUTX-703 is undergoing its first human trials. As this is an early-stage study, detailed safety information remains limited. The primary goal is to determine a safe dose for individuals with advanced blood cancers, such as acute myeloid leukemia (AML). The FDA has fast-tracked this treatment, indicating its potential promise.

Participants receive varying doses of AUTX-703 to assess tolerance without serious side effects. Researchers closely monitor for any adverse reactions. While comprehensive safety data is still forthcoming, careful dose adjustments aim to ensure the treatment's safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Researchers are excited about AUTX-703 because it offers a fresh approach to treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Unlike traditional chemotherapy, which broadly targets rapidly dividing cells, AUTX-703 is designed to be more selective, potentially reducing damage to healthy cells. This treatment is administered orally, making it more convenient than many existing treatments that require intravenous delivery. Additionally, the dosage flexibility—ranging from once to three times a week—allows for personalized treatment plans tailored to individual patient needs, which could enhance both safety and effectiveness.

What evidence suggests that AUTX-703 might be an effective treatment for acute myeloid leukemia and myelodysplastic syndrome?

Research has shown that AUTX-703 could be a promising treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Early results suggest that AUTX-703, a drug that breaks down certain proteins in cells, may help slow leukemia progression. In this trial, participants will receive varying dosages of AUTX-703 to evaluate its safety and effectiveness. The FDA has granted the drug fast track designation, which is given to treatments showing potential for serious conditions. Although clinical data is still being gathered, targeting specific proteins offers hope for those with advanced blood cancers. As more results emerge, optimism about its effectiveness grows. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced blood cancers like AML or MDS that haven't responded to, can't handle, or have refused standard treatments. It's also open to those who've relapsed after a stem cell transplant. Participants need to be in fair health (ECOG ≤2), with good liver, kidney, and heart function, and a WBC count ≤20 × 10⁹/L.

Inclusion Criteria

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)

I can take care of myself but might not be able to do heavy physical work.

My liver is functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating dosages of AUTX-703 to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)

Varies

Weekly visits

Dose Optimization

Participants receive AUTX-703 at selected dosages to further evaluate safety, PK, PD, and efficacy

Varies

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AUTX-703

Trial Overview The study tests AUTX-703 taken orally by patients with certain blood cancers. It aims to find out how safe it is, what the body does with it (PK), how it affects the body (PD), and if it shows any signs of working against the cancer.

How Is the Trial Designed?

Group I: Dose Optimization - Part B, Dosage 2 Experimental Treatment 1 Intervention

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.

Group II: Dose Optimization - Part B, Dosage 1 Experimental Treatment 1 Intervention

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.

Group III: Dose Escalation - Part A Experimental Treatment 1 Intervention

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).

Who Is Running the Clinical Trial?

Auron Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

The introduction of CPX-351, a liposomal formulation of daunorubicin and cytarabine, has significantly improved overall survival in patients aged 60-75 with newly diagnosed secondary and therapy-related acute myeloid leukemia (AML) compared to the traditional '7 + 3' regimen.

CPX-351 received FDA approval in August 2017, marking a significant advancement in AML treatment after decades of stagnation in therapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin-cytarabine liposome (CPX-351) in the management of newly diagnosed secondary AML: A new twist on an old cocktail. Maakaron, JE., Mims, AS.[2020]

CPX-351, a new liposomal formulation of daunorubicin and cytarabine, has been approved for treating newly diagnosed therapy-related acute myeloid leukemia (tAML) and AML with myelodysplasia-related changes, showing improved overall survival compared to the traditional '7+3' regimen.

This new treatment delivers a fixed 5:1 ratio of the two drugs, which may enhance efficacy, particularly in older patients who typically have poorer outcomes with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 daunorubicin-cytarabine liposome: a novel formulation to treat patients with newly diagnosed secondary acute myeloid leukemia. Cafaro, A., Giannini, MB., Silimbani, P., et al.[2020]

In 2017, the FDA approved five new drugs for treating acute myeloid leukemia (AML), including targeted therapies for specific genetic mutations (FLT3 and IDH2) and a new formulation of cytarabine-daunorubicin for certain types of AML.

The combination of the BCL-2 inhibitor venetoclax with low-intensity therapy showed promising results for older patients who are not suitable for intensive chemotherapy, indicating a shift towards more tailored treatment options in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Wei, AH., Tiong, IS.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06846606

Phase 1 Study of AUTX-703 in Relapsed/Refractory AML ... This is a first-in-human, Phase 1, multicenter study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary ...

2. aurontx.com aurontx.com/news/auron-announces-first-patient-dosed-in-phase-1-clinical-trial-of-autx-703-in-advanced-hematologic-malignancies

Auron Announces First Patient Dosed in Phase 1 Clinical ... AUTX-703 has cleared two INDs and is in a Phase 1 study in relapsed / refractory (r/r) AML and myelodysplastic syndromes (MDS). In addition, the ...

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/auron-autx-703/

First subject dosed in trial of Auron's AUTX-703 Auron has dosed the first subject in the Phase I trial of AUTX-703, targeting individuals with advanced haematologic malignancies.

4. onclive.com onclive.com/view/autx-703-receives-fda-fast-track-designation-in-relapsed-refractory-aml

AUTX-703 Receives FDA Fast Track Designation in ... AUTX-703, a KAT2A/B degrader, received FDA fast track designation for relapsed/refractory AML, with clinical trials starting in early 2025.

5. physicianresources.roswellpark.org physicianresources.roswellpark.org/news/phase-1-clinical-trial-offers-fda-fast-tracked-drug-for-relapsed/refractory-aml-and-mds

Phase 1 Clinical Trial Offers FDA Fast-Tracked Drug ... “Treatment with AUTX-703 suggests this novel agent could have potent effects on limiting leukemia progression, and we look forward to being one ...

6. targetedonc.com targetedonc.com/view/fda-fast-tracks-autx-703-in-relapsed-refractory-aml

FDA Fast-Tracks AUTX-703 in Relapsed/Refractory AML The FDA granted fast track designation to AUTX-703 for the treatment of patients with relapsed/refractory acute myelogenous leukemia (R/R AML).

7. mskcc.org mskcc.org/cancer-care/clinical-trials/25-141

A Phase 1 Study of AUTX-703 in People With Acute ... Researchers want to find the best dose of AUTX-703 to give safely in people with blood cancers. The people in this study have acute myeloid leukemia (AML) or ...