P1, N=36, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

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

P1, N=40, Recruiting, Marlise Luskin, MD | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2026

Additional studies evaluated the impact of strong CYP3A4 perpetrators and imatinib on a single 40 mg dose of asciminib. This PBPK model was applied in lieu of clinical pharmacology studies to support the new drug application of Scemblix® and to bridge data from 40 mg BID to the 80 mg QD and 200 mg BID dose regimens. The PBPK predictions informed the drug product label and are estimated to have replaced at least 10 clinical studies.

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

P4, N=85, Active, not recruiting, Novartis Pharmaceuticals | N=57 --> 85

Not available.

Combination therapies with ponatinib or other agents, as well as newer TKIs like olverembatinib, have demonstrated potential in overcoming resistance in preclinical and clinical models. Understanding these diverse resistance mechanisms is critical for optimizing asciminib-based treatment strategies and guiding the development of effective combination therapies for patients with resistant CML.

In this study, we employed molecular dynamics simulation to observe the synergistic interactions of BCR-ABL1 by the allosteric inhibitor asciminib and ATP competitive inhibitors nilotinib and ponatinib. Our study reveals the allosteric communication pathway between asciminib and ponatinib, providing more detailed insights into the effectiveness of combination therapy. These findings provide valuable insights into combination therapies, aiding in the rational use of medications and guiding the design of novel inhibitors.

P2, N=34, Active, not recruiting, Novartis Pharmaceuticals | N=195 --> 34

P4, N=57, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=85 --> 57

Overall, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well-tolerated and effective. Results were consistent among subgroups, indicating that asciminib is an effective option for patients regardless of prior TKI used, and including those intolerant or resistant to their first TKI.