Aspacytarabine for acute myeloid leukemia showed a complete response rate of 37% in phase 2 study.
Aspacytarabine (BST-236) for the treatment of newly diagnosed acute myeloid leukemia patients (AML) who are unfit for standard induction therapy, demonstrated acceptable safety, efficacy, and tolerability, according to a press release by Biosight Ltd.
Aspacytarabine is a novel anti-metabolite composed of cytarabine covalently bound to asparagine, thus acting as a prodrug of cytarabine. Cytarabine has been a main part of AML treatment for 45 years due to efficacy. However, it is associated with severe bone marrow, neurological, and gastrointestinal toxicities, limiting its use. Aspacytarabine allows for high-dose therapy with lower systemic exposure to free cytarabine while relatively sparing normal tissue.
The phase 2 trial (NCT03435848) of the agent had an estimated enrollment of 65 participants and an estimated study completion date of 2022. The primary end point of the study is complete remission 28 to 35 days after induction.
During the study, patients receive 1 to 4 courses of aspacytarabine Intravenously at 4.5 g/m2/d or 2.5 g/m2/d, for 6 days.
According to data presented at the 2021 American Society of Hematology Annual Meeting and Exposition, at the time of data cutoff, 65 patients from the phase 2b study with AML were included in the safety and efficacy analysis. All patients were unfit for standard induction chemotherapy and had a median age of 75 years. Thirty-eight percent of patients had an ECOG performance status of 2, 40% had secondary AML, and 17% received prior hypomethylating agents with or without venetoclax treatment.
The complete response rate was 37% across all evaluable patients, 27% in patients who received prior hypomethylating agents with or without venetoclax treatment, 44% in de novo AML patients, and 27% in secondary AML patients. Half of all evaluable complete responses were minimal residual disease negative. Additionally, rapid complete hematological recovery was observed in all patients who achieved a complete bone marrow response, with a median time of 25 days for complete neutrophil recovery. A complete platelet recover was observed for 26 days.
“These final complete remission data are extremely encouraging and strengthen our conviction in the potential of aspacytarabine as a potential standard-of-care treatment option for AML patients,” said Jessica Altman MD, professor, medicine, Hematology Oncology Division, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and lead study investigator in a press release. “Notably, a complete remission rate of 37% was achieved in a challenging patient population, including patients with secondary AML, prior hypomethylating agent treatment, and older age. While follow-up is still ongoing, the efficacy data across key measures, including duration of response and overall survival, combined with a favorable safety profile and a time-limited treatment of up to 4 courses, all form the basis for my confidence in aspacytarabine as a novel therapy for the treatment of patients with AML.”
In order to participate in the study, patients must be 18 years of age or older, not be eligible for standard induction therapy, and have an ECOG performance status of 2 or less at screening. Patients with relapsed or refractory AML, acute promyelocytic leukemia, an active malignant disease other than AML, congestive heart failure, or a life expectancy of less than 3 months are not eligible to participate.
“We continue to be very encouraged by the promising results of this larger data set, reinforcing our belief that aspacytarabine has the potential to become standard of care in patients with AML and may address a significant unmet need for those unfit for intensive chemotherapy. These results strongly support the continued progression of our aspacytarabine clinical trial program, with the recently announced expansion into additional Phase 2 studies in patients with relapsed or refractory AML and myelodysplastic syndrome,” said Ruth Ben Yakar, PhD, chief executive officer of Biosight, in a press release.