RecruitingPhase 1Phase 2NCT05601726

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

First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 As Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.

Sponsor

Advanced BioDesign

Enrollment

36 participants

Start Date

Nov 8, 2022

Study Type

INTERVENTIONAL

Conditions

Myelodysplastic Syndromes Acute Myeloid Leukemia, Adult

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria4

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 Criteria16

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)

Interventions

DRUGABD-3001

Each patient will receive a fixed 4 hours-intravenous infusion dose of ABD-3001 once or twice a week. For SAD : The first dose of the first cohort will receive an estimated infusion dose of 18 mg/m² at Day 1. Subsequent cohorts will be given the following doses: 54 mg/m², 135 mg/m², 270 mg/m², 405 mg/m², 540 mg/m².

DRUGABD-3001

For MAD : Based on all data gathered during the SAD including safety, PK and preliminary efficacy data, up to three doses were selected in accordance with the Safety review Committee (SRC). A dosage optimization analysis was performed at the end of the SAD cohort 6 using population pharmacokinetic modelling to set the optimal frequency of infusion per week for each selected dose to achieve sustained exposition throughout the treatment period. Based on this analysis, the Sponsor, in agreement with the SRC, defined 3 doses regimens that will be set up in parallel, with infusion of ABD-3001 once or twice a week during 3 cycles of 28 days.