A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP
Summary
The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected Tyrosine Kinase Inhibitor (TKI) for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the following treatment options for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD. This study has three periods: 1. Treatment period for all randomized participants, 2. Optional Treatment-Free Remission (TFR) period only for participants meeting TFR eligibility criteria and 3. Treatment Re-Initiation (TRI) period only for participants who relapsed after TFR attempt.
Timeline
- Start
- 2021-10-06
- Primary completion
- 2023-11-28
- Completion
- 2031-01-18
Outcome
Met primary endpoint
registry analysis (superiority test); Asciminib (All Asciminib ) vs Investigator Selected TKI (All Comparators); p <0.001; Risk Difference (RD) 18.88 (95% CI 9.59 to 28.17) NCT04971226 ↗
registry analysis (superiority test); Asciminib (Imatinib Stratum) vs Investigator Selected TKI (Imatinib Stratum); p <0.001; Risk Difference (RD) 29.55 (95% CI 16.91 to 42.18) NCT04971226 ↗
paper asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. PMID 41397287 ↗
release “In the study, Scemblix demonstrated superior MMR rates in both primary endpoints at week 48 vs. IS SoC TKIs and imatinib alone” novartis.com ↗
Publications
- Takahashi N, Kim DW, Kim I, Du X, Lee SE, Hu Y, Kikushige Y, Jiang Q, Wang Y, Chen S, Zhu H, Goto T, Tomita A, Ichii M, Nakamae H, Liu L, Liu B, Malek K, Zhu T, Wu S, Wang J. Asciminib Provides Better Efficacy and Favorable Safety and Tolerability Against Investigator-Selected Tyrosine Kinase Inhibitors in East Asian Patients With Newly Diagnosed Chronic Myeloid Leukemia: Results From a Subgroup Analysis of the Pivotal ASC4FIRST Study. Cancer Med. 2026 Jun;15(6):e72019. doi: 10.1002/cam4.72019.
- Cortes JE, Hughes TP, Wang J, Kim DW, Kim DDH, Mayer J, Goh YT, le Coutre P, Etienne G, Kim I, Andorsky DJ, Bombaci F, Issa GC, Takahashi N, Kapoor S, Jinwal R, Malek K, McCulloch T, Yau L, Larson RA, Hochhaus A. Asciminib demonstrates superior efficacy and safety in newly diagnosed chronic myeloid leukemia in the ASC4FIRST trial. Blood. 2026 Mar 26;147(13):1433-1446. doi: 10.1182/blood.2025029210.
- Hochhaus A, Wang J, Kim DW, Kim DDH, Mayer J, Goh YT, le Coutre P, Takahashi N, Kim I, Etienne G, Andorsky D, Issa GC, Larson RA, Bombaci F, Kapoor S, McCulloch T, Malek K, Yau L, Ifrah S, Hoch M, Cortes JE, Hughes TP; ASC4FIRST Investigators. Asciminib in Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med. 2024 Sep 12;391(10):885-898. doi: 10.1056/NEJMoa2400858. Epub 2024 May 31.
- Cortes JE, Hochhaus A, Takahashi N, Larson RA, Issa GC, Bombaci F, Ramscar N, Ifrah S, Hughes TP. Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. Future Oncol. 2022 Dec;18(38):4161-4170. doi: 10.2217/fon-2022-0923. Epub 2022 Dec 16.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Asciminib | Unknown | 80 mg | Oral |
| Comparator | Bosutinib | Small molecule | 400 mg | Oral |
| Comparator | Imatinib | Small molecule | 400 mg | Oral |
| Comparator | Nilotinib | Small molecule | 300 mg | Oral |
| Comparator | dasatinib anhydrous | Small molecule | 100 mg | Oral |