First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients (ODYSSEY)

Advanced BioDesign

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Myeloid Leukemia, Adult; Myelodysplastic Syndromes

Treatments: Drug: ABD-3001

Study type: Interventional

Funder types: Industry

Identifiers

NCT05601726

ABD3001CLIN1

Details and patient eligibility

About

This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part.

Full description

This FIH study combines, in patients with primary refractory or relapsed AML patients and in patients with high risk MDS a Single Ascending Dose (SAD) part (Part A) and a Multiple Ascending Dose (MAD) part (Part B).

The objective of the SAD phase is to explore a wide range of dose administered as a single and fixed 4-hours intravenous infusion in order to select a dose and a dosing frequency (determined using pharmacokinetic and pharmacodynamics parameters).

The objective of the MAD is to elucidate the pharmacokinetic (PK) and pharmacodynamics (PD) of multiple doses of ABD-3001. The dose levels and dosing intervals (i.e., time between consecutive doses) will be selected as those that are predicted to be safe from the SAD. Dose levels and dosing frequency will be derived from data obtained during the SAD.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with relapsed/refractory Acute Myeloid Leukemia (AML) after failing at least one therapy regimen and a salvage treatment or are not eligible for salvage treatment regimens including targeted therapy
• Patients with relapsed/refractory Myelodysplastic syndrome (MDS) ineligible for salvage treatment who are diagnosed high-risk and very high-risk using Revised International Prognostic Scoring System (IPSS-R) prognostic risk categorization
• Patients not eligible to alloSCT
• Negative blood or serum/urine pregnancy test

Exclusion criteria

• Patients with acute myeloid leukemia (AML) with Inv(16) MYH11-CBF-Beta or t(8;21) AML-ETO RUNX1-RUNX1 or (PML/RARA) karyotype abnormalities and eligible to targeted therapies
• Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia
• Ongoing immunosuppressive treatment
• Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to study Visit 1
• Active infection requiring intravenous anti-infectious treatment during the screening period
• Life-threatening illnesses other than the studied one, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety or interfere with the patient's ability to comply with the study activities
• Anti-tumor therapy within 14 days of study Visit 1
• Prior participation in an interventional investigational clinical study (drug or medical device) within 21 days of study Visit 1
• Radiotherapy within 28 days prior to study Visit 1
• Current history of seropositivity to human immunodeficiency virus (HIV) or infection with active hepatitis C virus (HCV) or active hepatitis B virus (HBV) or active SARS-CoV-2 (Covid-19) or Syphilis, or Cytomegalovirus (CMV), or Epstein-Barr virus (EBV), or Human T-Lymphotropic Virus (HTLV1)
• History of other malignancy in the last 12 months prior to study Visit 1
• Other active solid tumor
• Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or Left Ventricular Ejection Fraction (LVEF) <50% attested by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days of C1D1 prior to study Visit 1 (Day 1, start of study therapy)
• Subjects with a history of myocardial infarction within the last 3 months prior to study Visit 1 (Day 1, start of study therapy)
• Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events
• Major surgery within 4 weeks prior to study Visit 1 (Day 1, start of study therapy)
• Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial MAD specific exclusion criteria: Patients who have been part of SAD and have experienced a DLT.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

36 participants in 2 patient groups

Single Administration Dose (SAD) of ABD-3001

Experimental group

Description:

Dose escalation of 6 doses level using a 3+3 design.

Treatment:

Drug: ABD-3001

Drug: ABD-3001

Multiple Administration Dose (MAD) of ABD-3001

Experimental group

Description:

3 doses regimens in parallel during 3 cycles of 28 days

Treatment:

Drug: ABD-3001

Drug: ABD-3001