Novartis today announced positive, longer-term results from the pivotal Phase III ASC4FIRST trial with asciminib showing superior major molecular response (MMR) rates at week 961.

The study compared the MMR rate of asciminib 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 leukaemia 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 asciminib MMR rate vs. SoC, vs. imatinib and vs. 2G TKIs (nilotinib, dasatinib and bosutinib)1. Results were presented at the 66th 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 asciminib as a potentially practice-changing treatment option.”

The median follow-up was 2.2 years for asciminib and investigator-selected SoC TKIs1. Over 22% more patients treated with once-daily asciminib 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 asciminib MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%)1. Patients treated with asciminib also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs.

The safety profile of asciminib 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 asciminib, and discontinuation due to AEs was more than 50% lower for asciminib vs. both imatinib and 2G TKIs. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash 

Novartis also presented today at ASH interim data from the Phase II ASC2ESCALATE dose-escalation study in both the second line (2L) and newly diagnosed Ph+ CML-CP settings5. In the analysis of 2L patients at week 24 (n=28) asciminib demonstrated MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%), with a consistent safety and tolerability profile5. The most common AEs (>15%) were nausea, hypertension, and vomiting5.

“Novartis’ decades-long work in CML and deep relationships within the community have informed our asciminib clinical trial program of over 10 years, the centerpiece of our continuing drive to address ongoing unmet medical needs for people with CML,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “These latest findings reinforce the differentiated efficacy, safety and tolerability profile of Scemblix in newly diagnosed and previously treated adult CML patients.”

Asciminib was recently granted accelerated approval in the US to treat newly diagnosed adults with Ph+ CML-CP, which together with its approval in previously treated adult patients with Ph+ CML-CP expands the population of asciminib-eligible patients by four-fold. In addition, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of CML, recommending asciminib as a category 1 – preferred treatment for newly diagnosed Ph+ CML-CP and across all risk categories.

Source: Novartis