Longer term results from phase III ASC4FIRST trial with Scemblix (asciminib) showing superior major molecular response rates at week 96 – Novartis

Novartis announced positive, longer-term results from the pivotal Phase III ASC4FIRST trial with Scemblix (asciminib) showing superior major molecular response (MMR) rates at week 96 . The study compared the MMR rate of Scemblix to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) at the week 96 evaluation, the study’s key secondary endpoints. The longer-term results showed an increasing difference in Scemblix MMR rate vs. SoC, vs. imatinib and vs. 2G TKIs (nilotinib, dasatinib and bosutinib). Results were presented at the 66^th American Society of Hematology Annual Meeting & Exposition (ASH).

“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,” said Jorge Cortes, M.D., Director, Georgia Cancer Center. “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.”

The median follow-up was 2.2 years for Scemblix and investigator-selected SoC TKIs. Over 22% more patients treated with once-daily Scemblix achieved MMR at week 96 vs. all investigator-selected SoC TKIs, and nearly 30% more patients achieved MMR at week 96 vs. imatinib alone. The Scemblix MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%). Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs.

The safety profile of Scemblix at 96-weeks was consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date. Fewer grade ≥3 AEs and dose adjustments to manage AEs were reported for Scemblix, and discontinuation due to AEs was more than 50% lower for Scemblix vs. both imatinib and 2G TKIs. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash.