お知らせ • Jun 03
Novartis Reports 144-Week Data from Asc4first Trial of Scemblix Demonstrating Superior Efficacy and Safety in Newly Diagnosed Cml
Novartis announced positive 144-week data from the pivotal ASC4FIRST trial of Scemblix (asciminib) presented at the 2026 American Society of Clinical Oncology Annual Meeting. These results provide longer-term evidence that Scemblix demonstrated increasingly superior molecular responses at week 144 compared with established tyrosine kinase inhibitors (TKIs), strengthening confidence in its sustained response. ASC4FIRST compared the major molecular response (MMR) rate of Scemblix to investigator-selected standard-of-care TKIs (imatinib and second generation TKIs nilotinib, dasatinib, and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. The longer-term data showed a progressively larger difference in MMR rates favorable to Scemblix vs. standard-of-care TKIs, vs. imatinib and vs. second generation TKIs. In addition to meeting all primary and key secondary endpoints at weeks 48 and 96, Scemblix continued to extend the treatment benefit for patients vs. standard-of-care TKIs at week 144. At the cutoff, more patients remained on treatment with Scemblix vs. standard-of-care (78.6% vs. 55.9%), imatinib (81.2% vs. 50.0%), and second generation TKIs (76.0% vs. 61.8%). At week 144, nearly 24% more patients treated with Scemblix achieved MMR vs. all standard-of-care TKIs, and over 32% more patients achieved MMR vs. imatinib alone. The Scemblix MMR rate was 15.2% higher vs. second generation TKIs (75.0% vs. 59.8%; P=0.01*). Patients treated with Scemblix also achieved deeper molecular responses (MR4 and MR4.5) compared with standard-of-care TKIs. Secondary objectives MMR rates at week 144: 77.1% vs. 53.4% (Scemblix vs. investigator-selected standard-of-care TKIs), 79.2% vs. 47.1% (Scemblix vs. imatinib), 75.0% vs. 59.8% (Scemblix vs. second generation TKIs). MR4 at week 144: 55.7% vs. 36.3% (Scemblix vs. investigator-selected standard-of-care TKIs), 58.4% vs. 33.3% (Scemblix vs. imatinib), 53.0% vs. 39.2% (Scemblix vs. second generation TKIs). MR4.5 at week 144: 42.3% vs. 24.5% (Scemblix vs. investigator-selected standard-of-care TKIs), 43.6% vs. 19.6% (Scemblix vs. imatinib), 41.0% vs. 29.4% (Scemblix vs. second generation TKIs). Scemblix demonstrated a safety profile at 144 weeks consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date. Compared with both imatinib and second generation TKIs, Scemblix showed fewer grade =3 adverse events, fewer dose adjustments to manage adverse events, and more than 50% lower discontinuation due to adverse events. The most frequent adverse events (=15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash. Week 144: Grade =3 adverse events: Scemblix 49%, imatinib 52%, second generation TKIs 63%. Discontinuation due to adverse events: Scemblix 6%, imatinib 13%, second generation TKIs 14%. Adverse events leading to dose adjustments/interruptions: Scemblix 37%, imatinib 44%, second generation TKIs 63%. ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix 80 mg QD vs. investigator-selected first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected standard-of-care TKIs (imatinib, nilotinib, dasatinib, and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the second generation TKI stratum of (66% vs. 57.8%). The study remains ongoing with further efficacy and safety readouts planned. Scemblix is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature). Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive). In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Outside the US, Scemblix is approved to treat newly diagnosed adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in more than 60 countries, including the EU, China, and Japan. It is also approved in 61 countries, including the US and the EU, for previously treated adults with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, regardless of prior therapy, and in 58 countries, including the US and the EU, for patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with the T315I mutation.