Excellent efficacy and safety of aceminib in first-line chronic myelogenous leukemia

ASC4FIRST Results from a 96-week follow-up of a Phase 3 study (NCT04971226) evaluating Asciminib as a first-line treatment for patients with chronic phase chronic myeloid leukemia (CP-CML) compared with investigator's choice of TKIs, including imatinib and second-generation TKIs.

The U.S. Food and Drug Administration (FDA) approvedaceminib in October 2024 for the treatment of newly diagnosed adult patients with Philadelphia chromosome-positiveCP-CML based on 48-week major molecular response (MMR) data from the ASC4FIRST trial.

Subsequent analysis96-week follow-up highlighted thatmolecular response rates with aceminibcontinued to improve over time, with significant superiority observed in both preliminary and exploratory comparisons. Notably, he reported that although the study did not compare with second-generation TKIs, aceminib appeared to show better efficacy in this subgroup, further strengthening its potential as a first-line treatment.

Data presented at the 2024 ASH Annual Meeting showed that the MMR rate at week 96 was still higher in patients treated with aximinib (n=201) than in patients treated with the investigator's choice of TKI. The 96-week MMR rates were 74.1% and 52.0% respectively, with a difference of 22.4% (95%CI, 13.6%-31.3%; P<0.001). This represents an increase in MMR, as the 48-week MMR rates were 67.7% and 49.0%, respectively, initially meeting the trial's primary endpoint.

Safety data showed that aximinib was well tolerated, with only 5% of patients discontinuing treatment due to adverse reactions (AEs), compared with 12.9% for imatinib and second-generation TKIs. Additionally, aceminib was associated with fewer grade 3 or 4 AEs, fewer dose reductions, and fewer treatment interruptions compared with other TKIs. Importantly, he stressed, the median daily dose of aceminib was 80 mg/day, reflecting its good tolerability.

The safety analysis also showed that aximinib had comparable or lower rates of overall and grade 3/4 adverse events compared with imatinib. These differences were even more pronounced when comparing Asiminib with second-generation TKIs, in which nearly all adverse events occurred less frequently with Asiminib, further underscoring its favorable risk-benefit.

Reference materials:https://www.onclive.com/view/dr-cortes-on-asciminib-s-superior-efficacy-and-safety-in-first-line-cml