Scemblix (asciminib)

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

All TKIs are not recommended during the first trimester due to their risk of teratogenesis, but imatinib and nilotinib may be cautiously used from Weeks 16-18 onward. Non-TKI therapies, such as hydroxyurea and interferon-α, are considered safe throughout pregnancy. Data on ponatinib and asciminib remain insufficient to allow the safe use of these agents during pregnancy. Future research should aim to improve treatment-free remission rates through novel agents and combination strategies to allow a higher proportion of younger patients to discontinue therapy. Clinicians should always counsel women on pregnancy risks during therapy while reassuring male patients of TKI safety when fathering children.

Notably, during treatment with tyrosine kinase inhibitors (TKIs), she became intolerant to first- and second-generation TKIs, including the branded and generic imatinib, nilotinib, and dasatinib, followed by progression into lymphoid blast phase. This case highlights the diagnostic challenges and therapeutic complexity of managing CML in the setting of multi-TKI intolerance. Importantly, it underscores the persistent molecular silence despite repeated RT-qPCR testing and the successful introduction of asciminib as a novel therapeutic alternative.

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

In Japan, five agents-imatinib (Glivec®), dasatinib (Sprycel®), nilotinib (Tasigna®), bosutinib (Bosulif®), and STAMP inhibitor asciminib (Scemblix®)-are currently approved for first-line therapy. Looking forward, immunologic determinants of TFR and novel therapeutic approaches, including targeting CML stem cells with agents such as asciminib or demethylating drugs, may offer prospects for cure. This review summarizes the current evidence and practical considerations in selecting first-line therapy for chronic-phase CML, with a focus on optimizing long-term outcomes and advancing toward individualized and potentially curative strategies.