Scemblix (asciminib)

P4, N=200, Recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University o

P=N/A, N=200, Not yet recruiting, Novartis Pharmaceuticals

P2, N=50, Not yet recruiting, Novartis Pharmaceuticals

Asciminib has shown efficacy in heavily pretreated patients and in the first-line setting, but resistance and limited benefit after ponatinib highlight the need for new therapeutic options...TGRX-678 exhibits potent activity against wild-type and mutant ABL1, including T315I, synergism with orthosteric tyrosine kinase inhibitors (TKIs), central nervous system (CNS) penetration, and encouraging phase Ia/Ib clinical activity in heavily pretreated CML. Early but promising data are also emerging for TERN-701 from the CARDINAL trial...Key questions regarding durability, long-term safety, and optimal integration with ATP-competitive TKIs remain open. Ongoing trials will define the clinical role of these STAMPi and their potential to advance cure-directed strategies, including treatment-free remission.

Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the NR1I2 -25385C > T polymorphism and the body weight of the patient; however, further prospective studies are necessary.

P2, N=55, Enrolling by invitation, SWOG Cancer Research Network | Not yet recruiting --> Enrolling by invitation

Particular attention is paid to how STAMP inhibition differs from ATP-competitive TKIs in terms of selectivity, toxicity profile, and resistance patterns, and how asciminib can be positioned relative to ponatinib in later-line settings.Asciminib has established itself as an effective and generally well-tolerated option for patients with TKI-resistant or -intolerant CML and is poised to expand into earlier lines of therapy. Its ability to induce rapid and deep molecular responses with reduced off-target toxicity may have important implications for long-term disease control and future treatment-free remission (TFR) strategies. Ongoing studies will clarify its optimal sequencing, combination potential, and role in facilitating durable TFR.

P2, N=124, Completed, Novartis Pharmaceuticals | Trial completion date: Jul 2026 --> Oct 2025 | Trial primary completion date: Jul 2026 --> Oct 2025 | Active, not recruiting --> Completed

SiRNA-mediated FN1 knockdown reduced the cell's susceptibility to all generations of TKIs employed in treatment of CML, including asciminib...Clinically, deregulation of FN1 was also observed in peripheral blood cells derived from CML patients. Our data indicate that FN1 may serve as a potential therapeutic target to address TKI resistance or as a suitable biomarker for the treatment.

A personalized approach that takes into account the BCR::ABL1mutation profile is key to optimizing therapeutic strategies for CML. Further research is needed to more clearly define the mechanisms of resistance and the optimal sequence of use of available TKIs in clinical practice.

P=N/A, N=40, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Jul 2026 --> Dec 2026

P=N/A, N=201, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting