Posted: Tuesday, June 28, 2022
Based on the interim results of the phase Ib Beat AML trial, which were presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7027), treatment with 37 mg/day of the AXL kinase inhibitor plus decitabine demonstrated preliminary clinical activity in older patients with TP53-mutated/complex karyotype acute myeloid leukemia (AML). However, according to Alice S. Mims, MD, of The Ohio State University Comprehensive Cancer Center, Columbus, and colleagues, the toxicity profile and correlative data supported the reduction of the recommended phase II dose to 25 mg/day.
In phase Ib, seven newly diagnosed patients were administered 37 mg/day of TP-0903 plus 20 mg/m2 of decitabine; no dose-limiting toxicities were observed. Nine additional patients were treated in phase II before concerns of delayed blood cell count recovery resulted in dose reduction to 25 mg/day.
The composite complete remission rate in the 16 patients treated with 37 mg/day was 37.5%, including 1 patient with complete remission, 4 with complete remission with partial hematologic recovery, and 1 with complete remission with incomplete hematologic recovery; four patients achieved measurable residual disease negativity. Of the remaining 10 patients, 6.0% achieved a morphologic leukemia-free state, 37.5% had stable disease, 6.0% experienced treatment failure, and 12.5% were not evaluable due to withdrawal of consent or death from early disease progression. Two patients who achieved remission proceeded to stem cell transplantation.
Decreased neutrophil counts (37.5%), platelet counts (31.3%), and anemia (18.8%) were among the most commonly reported treatment-related adverse events of grade 3 or higher. A pharmacokinetic and correlative data analysis, which focused on soluble Axl and Gas6, also seemed to support dose reduction to 25 mg/day.
“The phase II study is ongoing to determine the clinical activity of this new recommended phase II dose,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.