Scemblix (asciminib)

P2, N=45, Not yet recruiting, University Health Network, Toronto

P=N/A, N=600, Recruiting, Novartis Pharmaceuticals | N=100 --> 600 | Trial completion date: Jul 2025 --> Jun 2030 | Trial primary completion date: Jul 2025 --> Jun 2030

P4, N=85, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Nov 2026 --> Mar 2026 | Trial primary completion date: Nov 2026 --> Mar 2026

We investigated the cytotoxic effects of ASC, alone or with imatinib (IM) or nilotinib (NIL), on committed progenitors and LSCs from CML patients expressing high or low BCR::ABL1 at diagnosis. When combined with IM or NIL, ASC restored TKI activity against LTC-ICs expressing high BCR::ABL1 transcripts, with the association of ASC and NIL reducing both LTC-IC division rates and LTC-IC-derived CFUs. These findings suggest that ASC, alone or with NIL, may target LSCs and improve outcomes in patients with high BCR::ABL1 expression at diagnosis.

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