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

Debiopharm

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Debio 1562M

Study type: Interventional

Funder types: Industry

Identifiers

NCT06969430

2024-519610-32 (Other Identifier)

Debio 1562M-101

U1111-1315-5913 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 134 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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134 participants in 3 patient groups

Phase 1 (Dose Escalation): Debio 1562M

Experimental group

Description:

Participants will receive Debio 1562M intravenously in escalating doses, once in every 3 weeks (Q3W), during each 21-day treatment cycle until progression of disease, unacceptable toxicity, participant's withdrawal, or Investigator's decision, or end of study whichever occurs first.

Treatment:

Drug: Debio 1562M

Phase 1 (Dose Optimization): Debio 1562M

Experimental group

Description:

Participants will be randomised 1:1 to receive 1 of the 2 Debio 1562M dose(s) and/or dosing schedule(s) selected based on the results from the Phase 1-Dose escalation for further investigation. Participants will be randomized to receive one of the 2 selected doses from Phase 1 (dose escalation) for further investigation and selection of recommended dose (RD) for Phase 2. Participants will receive Debio 1562M intravenously, once in every 3 weeks (Q3W), during each 21-day treatment cycle until progression of disease, unacceptable toxicity, participant's withdrawal, or Investigator's decision, or end of study whichever occurs first.

Treatment:

Drug: Debio 1562M

Phase 2: Debio 1562M

Experimental group

Description:

Participants will receive RD of Debio 1562M based on the results from Phase 1-Dose optimization. Participants will receive Debio 1562M intravenously, once in every 3 weeks (Q3W), during each 21-day treatment cycle until progression of disease, unacceptable toxicity, participant's withdrawal, or Investigator's decision, or end of study whichever occurs first.

Treatment:

Drug: Debio 1562M