Novartis' Scemblix (asciminib) continues to demonstrate superior efficacy and a favorable safety profile in adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP), according to 96-week data from the Phase III ASC4FIRST trial presented at the 66th American Society of Hematology Annual Meeting & Exposition (ASH). The study compared Scemblix to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, dasatinib, and bosutinib.
Sustained Efficacy of Scemblix
The longer-term results from the ASC4FIRST trial revealed an increasing difference in major molecular response (MMR) rates with Scemblix compared to SoC TKIs. At week 96, the MMR rate for Scemblix was 74.1% versus 52% for all investigator-selected TKIs (p<0.001). When compared to imatinib alone, Scemblix showed an even greater difference, with MMR rates of 76.2% versus 47.1% (p<0.001). Notably, Scemblix also demonstrated a clinically relevant 15.1% higher MMR rate compared to second-generation (2G) TKIs (72.0% vs. 56.9%).
According to Jorge Cortes, M.D., Director, Georgia Cancer Center, “These 96-week results are very encouraging for clinicians who aspire to obtain a balance of efficacy and tolerability profiles to help newly diagnosed adult CML patients achieve and maintain treatment goals. The sustained superior efficacy, deeper and more durable responses, and favorable safety and tolerability profile compared to standard of care TKIs continue to support the promise of Scemblix as a potentially practice-changing treatment option.”
Deeper Molecular Responses
Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs. At week 96, 48.8% of patients in the Scemblix arm achieved MR4, compared to 27.5% in the SoC TKI arm. Similarly, 30.9% of Scemblix-treated patients achieved MR4.5, versus 17.7% in the SoC TKI arm.
Favorable Safety and Tolerability
The safety profile of Scemblix at 96 weeks remained consistent with previous findings, showing no new safety concerns. Fewer grade ≥3 adverse events (AEs) and dose adjustments were reported for Scemblix. Discontinuation rates due to AEs were more than 50% lower for Scemblix compared to both imatinib and 2G TKIs. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash.
ASC2ESCALATE Phase II Study
Interim data from the Phase II ASC2ESCALATE dose-escalation study were also presented at ASH. In second-line (2L) patients, Scemblix demonstrated MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%) at week 24, with a consistent safety and tolerability profile. The most common AEs (>15%) in this study were nausea, hypertension, and vomiting.
Regulatory and Guideline Support
Scemblix was recently granted accelerated approval in the US for newly diagnosed adults with Ph+ CML-CP. The National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology, recommending asciminib as a category 1 – preferred treatment for newly diagnosed Ph+ CML-CP across all risk categories.
About the ASC4FIRST Trial
The ASC4FIRST trial (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study comparing oral Scemblix 80 mg QD to investigator-selected first- or second-generation TKIs in 405 adult patients with newly diagnosed Ph+ CML-CP. The trial met its primary endpoints, demonstrating superior MMR rates at week 48 with Scemblix versus SoC TKIs.
About Scemblix (asciminib)
Scemblix is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP inhibitor). Other approved CML treatments are TKIs that target the ATP-binding site. Scemblix is approved in the US for newly diagnosed and previously treated adults with Ph+ CML-CP and in other countries for patients previously treated with two or more TKIs.
