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.
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
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
Sequential
ABD-3001
DrugEach 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.
ABD-3001
DrugFor 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.
SAD : Estimation of the Maximum Tolerated Dose (MTD) of ABD-3001 as well as the doses and frequencies to be explored during the MAD
The primary endpoint is to assess the recommended dose range to be tested during the MAD by evaluation of incidence of patients who experienced Dose Limiting Toxicities (DLTs). according to CTCAE v5.0. The recommendation for doses to be tested during the MAD will be determined using all available data, which will include Dose Limiting Toxicities (DLTs), MTD if it has been reached, and other toxicities, signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.
MAD : To evaluate the safety, tolerability and to define a recommended dose range for further trials.
To assess the impact of ABD-3001 on safety and on its tolerability by evaluating: 1. Incidence of Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 Nov. 27, 2017)), timing, seriousness, and relationship to ABD-3001 either observed by the investigator during physical examination, or reported spontaneously by the patient, 2. Incidence of laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0 Nov. 27, 2017), and timing.
SAD : To evaluate the overall safety and tolerability profile of ABD-3001
To assess the impact of ABD-3001 on safety and on its tolerability by evaluating: 1. Incidence of Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 Nov. 27, 2017)), timing, seriousness, and relationship to ABD-3001 either observed by the investigator during physical examination, or reported spontaneously by the patient, 2. Incidence of laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0 Nov. 27, 2017), and timing,
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001
Maximum concentration (Cmax) of DIMATE and metabolites (CEY1410/H11)
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001
Time to maximum concentration (Tmax)
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001
Area Under the plasma Concentration versus time curve (AUC)
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