P2, N=69, Recruiting, Korean Society of Hematology | Not yet recruiting --> Recruiting

P=N/A, N=200, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Cumulative MR4.0 and MR4.5 rates by week 48 were 42.3% and 26.5%, respectively, with some patients harboring baseline BCR::ABL1 mutations showing these responses. These real-world outcomes support the safety and effectiveness of asciminib for patients with resistant/intolerant CML.

P2, N=125, Active, not recruiting, University of Jena | Not yet recruiting --> Active, not recruiting

P2, N=45, Not yet recruiting, The University of Hong Kong

P3, N=199, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

These data support that, considering its large therapeutic window, asciminib 200 mg twice daily can be used without any dose adjustment when co-administered with a strong CYP3A4 inducer drug. Furthermore, asciminib is not an OATP1B inhibitor up to this dose.

P1, N=12, Not yet recruiting, Washington University School of Medicine | Trial completion date: Aug 2027 --> Nov 2027 | Trial primary completion date: Jul 2027 --> Oct 2027

P3, N=406, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2028 --> Jan 2031

For resistance, assessment of BCR::ABL1 mutations is essential, and second-line agents should be chosen according to the initial TKI and mutation sensitivity. This article summarizes the criteria and timing for switching to second-line therapy and key considerations for selecting and managing second-line TKIs, and briefly reviews the evidence for asciminib and ponatinib in second-line and later settings.

Both primary patient and Ba/F3 cells carrying TPR::ABL2 exhibited kinase activation and sensitivity to tyrosine kinase inhibitors (TKIs). This study expands the repertoire of ABL2 fusions identified in ALL and supports the incorporation of TKIs into T-ALL treatment regimens to improve outcomes for this subtype.

The effectiveness of asciminib, combined with its capacity to overcome resistance through combination strategies with adenosine triphosphate-binding site tyrosine kinase inhibitors, establishes it as a focal point in emerging chronic myeloid leukemia treatment approaches. It remains essential to continue research and clinical trials to enhance the therapeutic efficacy of asciminib and manage its associated side effects.