Debio 1562M for people with relapsed or refractory acute myeloid leukemia

A Phase 1/2, First-in-human, Multicenter, Open-label Trial Evaluating the Safety, Tolerability, and Antileukemic Activity of Debio 1562M in Participants With Acute Myeloid Leukemia (AML)

This trial will try Debio 1562M to see if it is safe and can fight leukemia in people with relapsed or refractory AML who have no standard treatment options.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 134 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Debiopharm International SA (industry)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 7 sites (Duarte, California and 6 other locations)
• Trial ID: NCT06969430 on ClinicalTrials.gov

What this trial studies

The trial tests Debio 1562M in adults with relapsed or refractory acute myeloid leukemia, using a Phase 1 dose-escalation and dose-optimization sequence followed by a Phase 2 activity assessment. Phase 1 (Arm A) uses dose escalation to identify a recommended dose and then refines dosing in a dose-optimization cohort. Phase 2 enrolls participants at the selected dose to measure antileukemic activity and further characterize safety and tolerability. The multicenter study enrolls participants at major U.S. cancer centers and includes patients with prior autologous or allogeneic transplants if transplant-related criteria are met.

Who should consider this trial

Good fit: Adults with relapsed or refractory AML (excluding acute promyelocytic leukemia), an ECOG performance status of 0–2, resolved prior treatment toxicities, and no available standard therapies are the intended candidates.

Not a fit: People with acute promyelocytic leukemia, those with uncontrolled serious medical conditions, or those who do not meet safety or performance-status requirements may not benefit or be eligible.

Why it matters

Potential benefit: If successful, Debio 1562M could provide a new treatment option that induces remissions or controls disease in people with relapsed or refractory AML.

How similar studies have performed: Debio 1562M is a novel agent and while other early-phase targeted therapies have shown mixed but sometimes promising results in relapsed/refractory AML, public data specific to this compound are limited.

Eligibility criteria

Inclusion Criteria:

* For Phase 1-Dose escalation: Relapsed/refractory (R/R) AML (excluding acute promyelocytic leukemia) based on World Health Organization (WHO) Classification 2022 and relapsed/refractory higher-risk myelodysplastic syndrome (R/R HR -MDS) (includes high- and very high-risk MDS) as confirmed by the Revised International Prognostic Scoring System (IPSS-R) for whom no standard therapy of proven benefit is available.
* For Phase1-Dose optimization and Phase 2: R/R AML (excluding acute promyelocytic leukemia) based on world health organization (WHO) classification 2022 for whom no standard therapy of proven benefit is available.
* Eastern Cooperative Oncology Group performance (ECOG PS) status ≤2.
* Previous treatment-related toxicities must be resolved to ≤Grade 1 (excluding alopecia).
* Individuals with prior autologous or allogeneic bone marrow (BM) transplant are eligible.
* Prior allogeneic transplant must meet the following conditions: the transplant must have been performed more than 120 days before the first administration of Debio 1562M, the participant must not have ≥Grade 1 active graft versus host disease (GvHD) at the time of trial treatment start and must be off all immunosuppression for at least 2 weeks prior to starting treatment with Debio 1562M. Steroid use \[equivalent to ≤20 milligrams (mg) prednisone\] before and during the trial is allowed as long as this is not being used as post-transplant immunosuppression or graft versus host disease (GVHD) directed therapy.
* Adequate renal and hepatic function defined as:

  1. Estimated glomerular filtration rate (eGFR) ≥60 milliliter per minute (mL/min) based on the chronic kidney disease-Epidemiology Collaboration based on creatinine (CKD-EPIcr) 2021 equation.
  2. Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN).
  3. Serum total bilirubin level ≤1.5× ULN (for participants with Gilbert's syndrome or chronic blood transfusions, total bilirubin ≤3.0× ULN).

Exclusion criteria:

* Any prior exposure to cluster of differentiation (CD) 37 targeting agents.
* Clinically active infection including known active hepatitis B or C, human immunodeficiency virus infection, or cytomegalovirus or any other known concurrent infectious disease that, in the judgment of the Investigator, would make a participant inappropriate for enrollment into this trial (retesting not required).
* Clinically significant cardiac dysfunction within 6 months before enrollment including New York Heart Association Class III or IV heart failure, uncontrolled angina, myocardial infraction, severe uncontrolled ventricular arrhythmias, QT interval corrected for HR according to Fridericia's formula (QTcF) \>470 ms.
* Clinically significant and active cardiopulmonary disease.
* Other malignancies, except of:

  1. Hematologic malignancies other than those being investigated for which individuals are not on active antineoplastic therapy
  2. Nonhematologic malignancies in remission and for which individuals must have completed all antineoplastic therapy at least 6 months before trial treatment start and all treatment-related toxicities must have resolved to ≤Grade 1.
* Evidence for active central nervous system (CNS) leukemia involvement. If the participant has a prior history of CNS AML, the participant must have at least 2 negative cerebrospinal fluid (CSF) analyses and either a magnetic resonance imaging (MRI) or computed tomography (CT) (if MRI is not feasible) of the brain demonstrating no evidence of CNS disease.
* Evidence of peripheral neuropathy Grade ≥2.
* History of hypersensitivity to Debio 1562M (including its components), or any of its excipients.
* Treatment with any antileukemic therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic, or any investigational agent within 14 days or within 5 half-lives of the investigational treatment prior to first dose of trial treatment, whichever is shorter. Hydroxyurea may be given prior to and after trial treatment start for control of leukocytosis.
* Major surgery within 4 weeks prior to the start of treatment, or participant who have not recovered from side effects of the surgery.
* Pregnancy or breastfeeding.

Note: Other Inclusion/Exclusion criteria may apply.

Where this trial is running

Duarte, California and 6 other locations

• City of Hope Comprehensive Cancer Center — Duarte, California, United States (RECRUITING)
• Moffitt Cancer Center and Research Institute Hospital — Tampa, Florida, United States (RECRUITING)
• University of Chicago — Chicago, Illinois, United States (RECRUITING)
• START Midwest — Grand Rapids, Michigan, United States (RECRUITING)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (RECRUITING)
• The Ohio Sate University — Columbus, Ohio, United States (RECRUITING)
• MD Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Debiopharm International S.A

Conditions: Acute Myeloid Leukemia