Asciminib Demonstrated Better MMR Rates in Patients With Newly Diagnosed Ph+ CML-CP

Phase 3 trial results demonstrate that asciminib (Scemblix; Novartis) had better major molecular response (MMR) rates compared to standard of care tyrosine kinase inhibitor (TKI) treatment in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). The study, ASC4FIRST, is the first and only randomized study to compare a CML treatment with approved standard of care first- and second-generation TKIs.

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Asciminib is the first CML treatment that works by specifically targeting the ABL myristoyl pocket and was designed to be highly specific while reducing off-target kinase mediated effects. The reduction of effects results in an improved safety and tolerability profile, compared to current standard of care options. In addition, asciminib is a potential treatment option for patients who are resistant or experience intolerance to currently available TKI therapies. It is currently being studied across multiple treatment lines for Ph+ CML-CP as both a monotherapy and combination therapy.

“We are very encouraged by these results given that a significant proportion of patients with newly diagnosed chronic myeloid leukemia [CML] do not achieve their treatment goals,” said Tim Hughes, MD, professor, South Australian Health & Medical Research Institute, in a press release. “There remains a significant need in first-line therapy of CML for tolerable treatment options, allowing people with CML to balance their treatment alongside their quality of life.”

ASC4FIRST (NCT04971226) is a randomized, head-to-head, multicenter, open-label, phase 3 trial that compared 80-mg oral dose of asciminib to investigator-selected first- or second-generation TKIs—imatinib (Gleevec; Novartis), nilotinib (Tasigna; Novartis), dasatinib (Sprycel; Bristol Myers Squibb), or bosutinib (Bosulif; Pfizer)—in 405 adult patients with newly diagnosed Ph+ CML-CP. The 2 primary endpoints of the study are to compare the efficacy of asciminib with the investigator selected TKI. Secondary endpoints included safety and efficacy endpoints—MMR, MR4, MR4.5, complete hematological response, and BCR::ABL1 less than or equal to 1%—duration of and time to first MMR, MR4, and MR4.5, time to treatment failure, failure-free survival, progression-free survival, event-free survival, and overall survival. The study remains ongoing with a key secondary endpoint of proportion of patients that achieve MMR at week 96 and a safety endpoint of study treatment discontinuation due to adverse events (AEs).

The study findings demonstrated that both primary endpoints of MMR rate for asciminib compared with the investigator selected TKIs and compared to imatinib had shown both clinically and statistically significant results. In addition, asciminib demonstrated a favorable safety and tolerability profile with fewer AEs and treatment discontinuations than the standard of care TKIs. No new safety signals were shown in the ASC4FIRST data. Further, the trial remains ongoing, with more data to be presented at week 96, where the key secondary endpoint—MMR at week 96—and additional secondary endpoints will be evaluated.

“We are excited that [asciminib] may help people newly diagnosed with CML achieve their treatment goals while continuing to live their lives,” said Shreeram Aradhye, MD, president of development and chief medical officer, Novartis, in the press release. "Given the chronic nature of their condition, patients often need to be on TKI therapy for many years, so treatment options that are well tolerated and highly efficacious are crucial to support adherence."

Reference

Novartis. Novartis Scemblix® shows superior major molecular response (MMR) rates vs. standard‐of‐care TKIs in Phase III trial for newly diagnosed patients with chronic myeloid leukemia. News release. January 8, 2024. Access January 8, 2024. https://www.novartis.com/news/media-releases/novartis-scemblix-shows-superior-major-molecular-response-mmr-rates-vs-standard-care-tkis-phase-iii-trial-newly-diagnosed-patients-chronic-myeloid-leukemia