A Study to Assess the Safety, Tolerability, and Antileukemic Activity of Debio 1562M in Participants With Acute Myeloid Leukemia (AML)

Official title

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)

Overview

The primary purpose of Phase 1 is to assess the doses studied under Phase 1 (Dose Escalation) Arm A and identify the recommended dose (RD) for further development (Dose optimization). The primary objective of Phase 2 is to evaluate the antileukemic activity of Debio 1562M.

Interventions

• Drug Debio 1562M
  Administered as intravenous (IV) infusion

Primary outcome measures

• Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [Time frame: Up to Day 28]
• Phase 1: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to Day 219]
• Phase 1 (Dose Optimization): Recommended Dose (RD) of Debio 1562M [Time frame: Up to Day 198]

Secondary outcome measures (12)

• Phases 1 and 2: Overall Response (OR) [Time frame: Up to Day 198]
• Phases 1 and 2: Percentage of Participants with CR [Time frame: Up to Day 198]
• Phases 1 and 2: Percentage of Participants With CR+ CRh [Time frame: Up to Day 198]
• Phases 1 and 2: Percentage of Participants With Composite Complete Remission (cCR) [Time frame: Up to Day 198]
• Phases 1 and 2: Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplant (ASCT) [Time frame: Up to Day 198]
• Phases 1 and 2: Change From Baseline in Blood Blast Count [Time frame: Baseline upto Day 198]
• Phases 1 and 2: Duration of Remission (DOR) [Time frame: Up to Day 198]
• Phases 1 and 2: Relapse Free Survival (RFS) [Time frame: Up to Day 198]
• Phase 1 (Dose Optimization) and Phase 2: Event Free Survival (EFS) [Time frame: Up to Day 198]
• Phase 1 (Dose Optimization) and Phase 2: Overall Survival (OS) [Time frame: Up to Day 198]
• Phases 1 and 2: Plasma Concentration of Debio 1562M and its Metabolites [Time frame: Pre-dose and at multiple time points up to Day 198]
• Phase 1 (Dose Optimization) and Phase 2: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) [Time frame: Up to Day 219]

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:

• 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.
• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN).
• 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:

• Hematologic malignancies other than those being investigated for which individuals are not on active antineoplastic therapy
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• City of Hope Comprehensive Cancer Center — Duarte
• Moffitt Cancer Center and Research Institute Hospital — Tampa
• University of Chicago — Chicago
• START Midwest — Grand Rapids
• Roswell Park Comprehensive Cancer Center — Buffalo
• The Ohio Sate University — Columbus
• MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT06969430 · Debio 1562M-101 · 2024-519610-32 · U1111-1315-5913

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗