Scemblix, with novel mechanism of action, shows superior, long-term efficacy and consistent tolerability in 96-week follow-up of phase III ASCEMBL trial for chronic myeloid leukemia

In this analysis, the proportion of patients in the Scemblix (asciminib) arm (n=157) who achieved a major molecular response (MMR) at 96 weeks was more than double that in the Bosulif (bosutinib) arm (n=76) (37.6% vs. 15.8% [P=.001]), substantially increasing from previous analyses. Additionally, the probability of maintaining MMR for at least 72 weeks for patients treated with Scemblix was 96.7% (95% CI, 87.4%–99.2%), reflecting long-term durability of efficacy. Despite longer duration of exposure for patients in the Scemblix arm – with a median of 23.7 months vs. 7.0 months for patients in the Bosulif arm – the updated 96-week analysis showed the proportion of patients treated with Scemblix who discontinued treatment due to adverse events (AEs) continued to be more than three times lower than those treated with Bosulif (7.7% vs. 26.3%). No new on-treatment deaths were reported since the primary analysis at 24 weeks.

“In a chronic cancer where resistance can develop to many of the existing therapies, or where patients can have their quality of life negatively impacted by treatment side effects over time, it’s encouraging to see sustained and increasing efficacy with consistent adequate tolerability for patients treated with Scemblix in the longer term,” said Jorge E. Cortes, MD, Director, Georgia Cancer Center, Augusta University. “This 96-week data shows the potential of Scemblix and its unique mechanism of action to help change the treatment paradigm in CML.”

Scemblix is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket. With this novel mechanism of action, it is also known in scientific literature as STAMP inhibitor, Scemblix can help address resistance to TKI therapy in patients with Ph+ CML-CP and overcome mutations at the defective BCR-ABL1 gene, which is associated with the over-production of leukemic cells. Scemblix continues to be studied across multiple lines of treatment for CML-CP11-18.

In addition to durable responses consistent with the primary analysis, more patients treated with Scemblix than Bosulif had BCR:ABL1 less than 1% (45.1% vs 19.4%) at 96 weeks. The most frequent (less than 10% in any treatment arm) grade greater than 3 AEs on Scemblix vs. Bosulif, respectively, were thrombocytopenia (22.4%, 9.2%), neutropenia (18.6%, 14.5%), diarrhea (0%, 10.5%), and increased alanine aminotransferase (0.6%, 14.5%). The values for these AEs were similar to the values reported at the 24 and 48 week analyses.