ASC4FIRST Trial: Asciminib Shows Favorable Safety, Efficacy Versus Investigator-Selected TKIs in CML

Asciminib showed superior safety and efficacy compared with standard-of-care, second-generation, investigator-selected tyrosine kinase inhibitors (TKIs) in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP), according to results of the phase III ASC4FIRST study presented at the 66th American Society of Hematology Annual Meeting & Exposition.

Adult patients with newly diagnosed CML-CP were stratified by European Treatment and Outcome Study (EUTOS) long-term survival risk score and treatment type (imatinib or investigator-selected TKI [nilotinib, dasatinib, or bosutinib]). Patients were randomized 1:1 to receive asciminib 80 mg once daily, or a second-generation investigator-selected TKI.

The primary endpoints were molecular response (MMR) rate at weeks 48 and 96. The secondary safety endpoint was time to treatment discontinuation due to adverse events (AEs). A total of 201 patients in the asciminib group and 204 patients in the investigator-selected TKI group were included in the efficacy analysis. A total of 200 patients receiving asciminib, 99 patients receiving imatinib, 49 receiving nilotinib, 42 receiving dasatinib, and 11 receiving bosutinib were included in the safety analysis.

At week 48, 86% of patients receiving asciminib, 62% receiving imatinib, and 75% receiving second-generation TKIs continued treatment. The MMR rate at week 48 was superior with asciminib versus second-generation investigator-selected TKIs (67.7% vs 49.0%, respectively; 95% CI, 9.6-28.2; adjusted 2-sided P<.001) and with asciminib versus imatinib (69.3% vs 40.2%, respectively; 95% CI, 16.9-42.2; adjusted 2-sided P<.001). The rate of optimal response was also higher with asciminib versus TKIs at week 12 (89.6% vs 70.1%, respectively) and week 24 (88.6% vs 63.7%, respectively).

Asciminib also had a better safety profile than imatinib and investigator-selected TKIs. Grade 3 or higher AEs occurred in 38.0% of patients receiving asciminib, 44.4% receiving imatinib, 51.0% receiving nilotinib, 54.8% receiving dasatinib, and 72.7% receiving bosutinib. AEs led to treatment discontinuation in 4.5% of patients receiving asciminib, 11.1% receiving imatinib, 8.2% receiving nilotinib, 11.9% receiving dasatinib, and 9.1% receiving bosutinib. AEs of any grade that led to dose adjustments or interruptions occurred in 30.0% of patients receiving asciminib, 39.4% receiving imatinib, 49.0% receiving nilotinib, 54.8% receiving dasatinib, and 63.6% receiving bosutinib.

“[Asciminib’s] superior efficacy versus all [investigator-selected] TKIs and more favorable safety/tolerability compared with each [investigator-selected] TKI suggests that [asciminib]  may transform the CML [treatment] paradigm,” the researchers concluded.

Reference

Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study. Abstract #475. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.