NCT06969430招募中1 期
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)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 154
- 试验地点
- 12
- 主要终点
- Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The primary purpose of Phase 1 is to characterize the safety and tolerability to identify the recommended dose (RD) of Debio 1562M for further development.
The primary objective of Phase 2 is to evaluate the antileukemic activity of Debio 1562M.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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).
排除标准
- •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
- •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 ≥
- •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.
研究组 & 干预措施
Phase 2: Debio 1562M
Experimental
Participants will receive RD of Debio 1562M based on the results from Phase 1-Dose optimization.
干预措施: Debio 1562M (Drug)
Phase 1 (Dose Escalation): Debio 1562M
Experimental
Participants will receive Debio 1562M intravenously in escalating doses, once in every 3 weeks (Q3W) and once in every week (QW), 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.
干预措施: Debio 1562M (Drug)
Phase 1 (Dose Optimization): Debio 1562M
Experimental
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.
干预措施: Debio 1562M (Drug)
结局指标
主要结局
Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
时间窗: Up to Day 28
Phase 1: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
时间窗: Up to Day 219
Phase 1 (Dose Optimization): Recommended Dose (RD) of Debio 1562M
时间窗: Up to Day 198
Phase 2: Percentage of Participants With Complete Remission (CR) + CR with partial hematological recovery (CRh)
时间窗: Up to Day 198
次要结局
- Phases 1 and 2: Overall Response (OR)(Up to Day 198)
- Phases 1 and 2: Percentage of Participants with CR(Up to Day 198)
- Phases 1 and 2: Percentage of Participants With CR+ CRh(Up to Day 198)
- Phases 1 and 2: Percentage of Participants With Composite Complete Remission (cCR)(Up to Day 198)
- Phases 1 and 2: Percentage of Participants With Allogeneic Hematopoietic Stem Cell Transplant (ASCT)(Up to Day 198)
- Phases 1 and 2: Change From Baseline in Blood Blast Count(Baseline upto Day 198)
- Phases 1 and 2: Duration of Remission (DOR)(Up to Day 198)
- Phases 1 and 2: Relapse Free Survival (RFS)(Up to Day 198)
- Phase 1 (Dose Optimization) and Phase 2: Event Free Survival (EFS)(Up to Day 198)
- Phase 1 (Dose Optimization) and Phase 2: Overall Survival (OS)(Up to Day 198)
- Phases 1 and 2: Plasma Concentration of Debio 1562M and its Metabolites(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)(Up to Day 219)
- Phase 1: Percentage of Participants With CR+ CRh(Up to Day 198)
研究者
研究点 (12)
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