Dr Hughes on Efficacy Data for Asciminib in Newly Diagnosed Ph+ CP-CML

Timothy Hughes, MD, MBBS, FRACP, FRCPA, clinical director, Precision Cancer Medicine Theme at SAHMRI, consultant hematologist, Royal Adelaide Hospital discusses efficacy findings from the phase 3 ASC4FIRST trial (NCT04971226) evaluating asciminib (Scemblix) vs investigator-selected TKIs in patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic-phase chronic myeloid leukemia (CP-CML).

The study randomly assigned patients at least 18 years of age with Ph-positive CP-CML to receive asciminib or investigator’s choice of TKI. Both arms included an imatinib (Gleevec) stratum and a second-generation TKI stratum.

Findings presented at the 2024 ASCO Annual Meeting showed that the study met its co-primary end points. At week 48, patients treated with asciminib (n = 201) experienced a major molecular response rate (MMR) of 67.7% compared with 49.0% for patients treated with any investigator-selected TKI (n = 204; difference, 18.9%; 95% CI, 9.6%-28.2%; P < .001). Regarding the second primary end point of MMR at week 48 for patients treated with asciminib (n = 101) or an investigator-selected TKI (n = 102) within the imatinib stratum, the MRRs were 69.3% and 40.2%, respectively (difference, 29.6%; 95% CI, 16.9%-42.2%; P < .001).

Notably, MMR at week 48 for patients who received second-generation asciminib (n = 100) or a second-generation TKI (n = 102) was a key secondary end point. The MMR at week 48 was 66.0% for asciminib and 57.8% for second-generation TKIs (difference, 8.2%; 95% CI, –5.1% to 21.5%). Hughes notes that there was a numerical difference that was not statistically significant for this end point; however, he notes that the study was not powered to measure the statistical significance of this end point.

In his presentation, Hughes concluded by noting that these data could support asciminib as the therapy of choice in the first-line setting for patients with Ph–positive CP-CML, and longer-term follow-up will further elucidate the potential benefit of this therapy in this setting.