The ASCERTAIN trial, a pivotal Phase 3 study, compared the efficacy and safety of an oral fixed-dose combination of decitabine and cedazuridine (INQOVI®) with intravenous decitabine in adults suffering from intermediate and high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). This trial marked the first instance where pharmacologic equivalence was demonstrated between an oral and an intravenous formulation of a hypomethylating agent for these conditions.
Published in The Lancet Haematology, the trial reported a median overall survival (mOS) of approximately 32 months among the trial population. Additionally, the overall response rate stood at 62% in the intent-to-treat patient population. Notably, 20% of the trial participants proceeded to transplantation, a rate surpassing the expected transplantation rates for patients undergoing hypomethylating agent treatment for MDS and CMML.
Safety outcomes from the study were consistent with those previously observed with intravenous decitabine, with thrombocytopenia, neutropenia, and anemia being the most common treatment-emergent adverse events. These findings supported the approval of INQOVI® by the U.S. Food and Drug Administration and Health Canada in July 2020 for treating adult patients with MDS, including various subtypes and risk groups.
Dr. Guillermo Garcia-Manero, the lead author of the publication, highlighted the significance of the ASCERTAIN study in providing an alternative oral treatment option to the traditional parenteral administration of decitabine, potentially reducing the need for frequent office visits and travel for patients.
The ASCERTAIN trial was a multicenter, randomized, open-label, crossover pharmacokinetics study, comparing the oral fixed-dose combination of decitabine and cedazuridine to intravenous decitabine in the first two cycles of treatment. Patients continued with the oral combination from Cycle 3 onwards. The primary endpoint was the total 5-day area-under-the-curve (AUC) equivalence of the oral and intravenous formulations.
INQOVI® is indicated for the treatment of adult patients with MDS, including previously treated and untreated cases, and is the first and only oral hypomethylating agent approved by the FDA and Health Canada for intermediate and high-risk MDS, including CMML.
Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are serious conditions characterized by dysplastic changes in myeloid cells and cytopenias, with MDS potentially evolving into acute myeloid leukemia (AML) in one-third of patients. The development of an oral treatment option like INQOVI® represents a significant advancement in the management of these diseases, offering patients a more convenient treatment modality.
