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ASH 2025 | Phase I trial of ONC201 as post-transplant maintenance for AML and MDS
Vijaya Bhatt, MBBS, University of Nebraska Medical Center, Omaha, NE, discusses the results of a Phase I trial (NCT03932643) evaluating the novel first-in-class agent ONC201 as post-transplant maintenance therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Dr Bhatt highlights the agent’s manageable safety profile, low cytotoxic effect, and promising overall survival (OS) and relapse-free survival (RFS) rates observed in the study. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
Yeah, we conducted a phase one trial of DODA-B-prone or ONC201. It’s an oral weekly medicine. In preclinical studies, it has shown activity against leukemia cell lines regardless of TP53 mutation or complex karyotype. So we designed a trial to prevent post-transplant relapses in this high-risk population. So it was a single center phase one trial where we started with a lower dose of 250 milligrams and went up to a highest dose of 650 milligrams once a week...
Yeah, we conducted a phase one trial of DODA-B-prone or ONC201. It’s an oral weekly medicine. In preclinical studies, it has shown activity against leukemia cell lines regardless of TP53 mutation or complex karyotype. So we designed a trial to prevent post-transplant relapses in this high-risk population. So it was a single center phase one trial where we started with a lower dose of 250 milligrams and went up to a highest dose of 650 milligrams once a week. We determined that the drug is safe without any dose-limiting toxicities. The adverse event rates particularly grade 3 or higher adverse events were relatively low at 45%, 15% were considered related and that’s quite comparable to the post transplant complications we see in people without maintenance as well. One of the remarkable aspects of this drug is in preclinical studies it has shown to affect leukemia stem cells but not affect the normal bone marrow cells. So we expected that cytotoxic effect would be relatively low and in our trial we did find that grade 3 or 4 cytopenias were quite low at 10 to 15 percent which is much less than what we would expect for example with azacitidine. We also included other endpoints such as survival, relapse-free survival. At two-year overall survival was 70% which we think is promising given the high-risk nature of these patients and high likelihood of relapse. Relapse-free survival was 60%, non-relapse mortality was very low at about 6%, particularly in a predominantly older adults who had significant comorbidity burden and impaired physical function at the time of diagnosis. We also captured health-related quality of life and functional measures and demonstrated that both in terms of quality of life and changes in physical function, there were no significant decline on average. So that provided additional suggestion that the drug is well tolerated. So we hope to move it forward and consider a phase two trial in the future.
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