Novartis has unveiled promising, long-term results from the pivotal phase III ASC4FIRST trial with Scemblix (asciminib), illustrating superior major molecular response (MMR) rates at the 96-week mark. The research compared Scemblix’s MMR rate against investigator-chosen standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) like imatinib, nilotinib, dasatinib, and bosutinib, as well as imatinib alone, in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). These findings, which represent the study’s key secondary endpoints, demonstrate a growing gap in the MMR rate of Scemblix compared to SoC, imatinib, and second-generation TKIs (nilotinib, dasatinib, and bosutinib). These results were shared at the 66th annual meeting of the American Society of Hematology (ASH).
“These 96-week outcomes are encouraging for healthcare providers aiming for a balance between effectiveness and tolerability to assist newly diagnosed adult CML patients in achieving and maintaining their treatment goals,” stated Jorge Cortes, M.D., director at the Georgia Cancer Center. “The ongoing superior efficacy, more profound and sustained responses, and beneficial safety and tolerability compared to standard-of-care TKIs continue to highlight Scemblix’s potential as a groundbreaking treatment alternative.”
The median follow-up period was 2.2 years for both Scemblix and the selected SoC TKIs. Over 22% more individuals receiving once-daily Scemblix achieved MMR at 96 weeks compared to all investigator-chosen SoC TKIs, and nearly 30% more achieved MMR relative to imatinib alone. The MMR rate for Scemblix was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher compared to second-generation TKIs (72% vs. 56.9%). Scemblix-treated patients also attained deeper molecular responses (MR4 and MR4.5) in comparison to investigator-chosen SoC TKIs.
Additionally, Novartis presented interim results from the phase II ASC2ESCALATE dose-escalation study covering both the second-line (2L) and newly diagnosed Ph+ CML-CP scenarios. In the 2L patient analysis at the 24-week mark (n=28), Scemblix showcased MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%) with enduring safety and tolerability. The frequently seen adverse events (>15%) included nausea, hypertension, and vomiting.
“Novartis’ longstanding efforts in CML and robust connections within the community have shaped our decade-long Scemblix clinical trial initiative, central to our ongoing pursuit of addressing the unfulfilled medical needs of CML patients,” shared Jeff Legos, executive vice president and global head of oncology development at Novartis. “These new data solidify Scemblix’s distinct effectiveness, safety, and tolerability for both newly diagnosed and previously treated adult CML patients.”
Scemblix recently earned accelerated approval in the US for treating newly diagnosed adults with Ph+ CML-CP, expanding its eligibility alongside its approval for previously treated adults with Ph+ CML-CP by four-fold. Moreover, the National Comprehensive Cancer Network (NCCN) recently updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CML treatment, promoting asciminib as a category 1 preferred treatment for newly diagnosed Ph+ CML-CP, applicable across all risk levels.
The ASC4FIRST (NCT04971226) represents a phase III, head-to-head, multi-center, open-label, randomized study involving oral Scemblix (80 mg QD) versus first and second-generation TKIs (imatinib, nilotinib, dasatinib, or bosutinib) in 405 adult patients recently diagnosed with Ph+ CML-CP. This trial met both its primary endpoints, with Scemblix demonstrating superior MMR rates at the 48-week mark when compared to investigator-chosen SoC TKIs (imatinib, nilotinib, dasatinib, and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%), as well as meeting non-powered secondary endpoints for the 2G TKI stratum (66% vs. 57.8%). The study remains active with more efficacy and safety insights forthcoming.
Alternatively, the ASC2ESCALATE (NCT05384587) entails a phase II, multicenter, single-arm, dose-escalation study of oral Scemblix (80 mg QD) within the US, focusing on both second-line (2L) and newly diagnosed (1L) Ph+ CML-CP environments. Although already approved for diverse therapy lines, this is the debut trial evaluating asciminib in the 2L context and a dose-escalation plan for asciminib as 2L and 1L treatment in CML-CP patients not achieving molecular milestones. The main endpoint will gauge the proportion of 2L patients achieving MMR at 12 months. This study continues, with enrollment completed among 196 patients (100 in 2L, 96 in 1L).
Scemblix stands as the premier CML treatment specifically targeting the ABL Myristoyl Pocket, recognized scientifically as a STAMP inhibitor. Other approved CML therapies are ATP-competitive TKIs targeting the ATP-binding site.
In the US, Scemblix has received approval for treating newly diagnosed adults with Ph+ CML-CP and those previously treated with Ph+ CML-CP. Beyond the US, it is sanctioned in over 75 nations, inclusive of the EU, for treating individuals previously managed with two or more TKIs with Ph+ CML-CP. In specific regions, including the US, Scemblix also holds approval for patients with Ph+ CML-CP carrying the T315I mutation.
Scemblix is explored across diverse Ph+ CML-CP treatment stages, as a standalone therapy and in combination.
With a track record exceeding 20 years in CML, Novartis pledges ongoing efforts to resolve unmet patient needs and to diminish obstacles to patient access and cost, facilitating patient benefit from innovative solutions. Novartis offers Patient Support to assist eligible patients with navigating treatment initiation, insurance coverage comprehension, and potential financial aid identification.