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Venetoclax

Azacitidine

Cc-486

Onureg (CC-486, oral azacitidine) will be administered orally at 200 or 300 mg once daily for 7 or 14 consecutive days, beginning on Day 1 of repeated 28-day cycles.

Venetoclax will be administered orally at 400 mg once daily for 14 consecutive days on days 1 to 14, beginning on Day 1 of repeated 28-day cycles.

Patients will be treated up to 4 cycles and for a maximum of 24 cycles.

Onureg + Venetoclax

Fatiha CHERMAT

Magalie JORIS, MD

Magalie FOSSARD, MD

Sylvain THEPOT, MD

Thorsten BRAUN, MD/PhD

Sophie PARK, MD/PhD

Kamel LARIBI, MD

Laurent PASCAL, MD/PhD

Laurent Laurent, MD/PhD

Marie-Pierre GOURIN, MD

Gaëlle FOSSARD, MD

Colombe SAILLARD, MD

REZA TABRIZI, MD

Franciane PAUL, MD

Alice GARNIER, MD

Thomas CLUZEAU, MD/PhD

Pierre FENAUX, MD/PhD

Rudy BIRSEN, MD

Sophie DIMICOLI-SALAZAR, MD

Jose Miguel TORREGROSA DIAZ, MD

Aspasia STAMATOULLAS, MD

Thibault COMONT, MD

Emmanuel GYAN, MD/PhD

Clémence SANTANA, MD

Maud D'AVENI-PINEY, MD

Adrien CONTEJEAN, MD

Norbert VEY, MD/PhD

This phase I/II open-label, dose-finding, multi-center study will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with higher-risk myelodysplastic syndromes (HR-MDS) not eligible to transplant.

During phase I, three dose features of Onureg will be tested in combination with a fixed dose of Venetoclax to define the optimal biological dose for phase II.

The phase II will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with HR-MDS not eligible to transplant.

Oral Azacitidine Combined With Venetoclax in Previously Untreated Higher-risk Myelodysplastic Syndromes

A Phase I/II, Open-label, Single Arm, Multicenter Dose-finding Study Assess the Safety and Preliminary Efficacy of Oral Azacitidine CC-486 (ONUREG) in Combination With Venetoclax (VENCLYXTO) in Previously Untreated Higher-risk Myelodysplastic Syndromes Ineligible for Allogenic Transplantation

Determination of minimal Residual Disease (MRD) by Next Generation Sequencing (NGS) and dynamics of molecular alterations associated with MDS

Dose-limiting toxicities according to CTCAE (common terminology criteria for adverses events) 5.0 occurring within the first cycle of treatment

Overall response measured after the first cycle of treatment according to modified IWG-MDS (International Working Group-Myelodysplastic Syndromes) 2006 and IWG-HR-MDS 2023 criteria

Best response evaluated according to the modified IWG-MDS 2006 and IWG-HR-MDS 2023 criteria

Hematological improvement (erythroid, neutrophil and platelet improvement) according to IWG-MDS 2006 and IWG-HR-MDS 2023

Time from onset of treatment to date of achievement of any response according to the modified IWG-MDS 2006 criteria

Time interval between the first date of achievement of any response according to the modified IWG-MDS 2006 criteria to relapse

Time from onset of trial treatment to onset of subsequent therapy

Determination of overall survival rate, event-free survival rate, progression-free survival rate

Rate of red blood cells and platelets transfusion independance for transfusion-dependent patients at baseline

Time interval between the achievement of transfusion independence and relapse with need of transfusion

Toxicity profile of study treatment including identification and grading of adverse events based on NCI CTCAE version 5, cytopenia duration, life-threatening or fatal cytopenias rate, unscheduled hospitalization rate, infectious complications rate, red blood cells and platelets transfusions needs

Patient-reported outcomes according to Functional Assessment of Chronic Illness Therapy - anemia (FACIT-An) version 4 (Score range: 0-188), evaluation of of change in QoL from baseline

Determination of early mortality rate at day 28

Patient-reported outcomes according to 5-level EuroQol-5D (EQ-5D-5L) (Scale numbered from 0 to 100), evaluation of change in QoL from baseline

Patient-reported outcomes according to Patient global impression of change (PGIC) form, evaluation of change in QoL from baseline

Patient-reported outcomes according to Patient global impression of severity (PGIS) form, evaluation of change in QoL from baseline

Spots Global Cancer Trial Database for onureg + venetoclax