An updated analysis of the phase 3 ASCEMBL study demonstrated sustained efficacy and a favorable safety profile with asciminib compared with bosutinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) after 2 or more prior ATP-binding tyrosine kinase inhibitors (TKIs), according to results presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Michael J. Mauro, MD, leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center in New York, New York, presented the updated data, which demonstrated asciminib significantly improved the rate of major molecular response (MMR) at 48 weeks compared with bosutinib and was consistent with data from primary analysis at 24 weeks.
“Asciminib was recently approved by the [U.S. Food and Drug Administration] for the treatment of adults with Ph+ CML-CP previously treated with 2 or more TKIs and in those with T315I mutation,” Dr Mauro said. “We report updated efficacy and safety results for patients in ASCEMBL.”
The trial (ClinicalTrials.gov Identifier: NCT03106779) included 233 patients with CML-CP previously treated with 2 or more TKIs and randomly assigned them in a 2:1 ratio to receive asciminib 40 mg twice daily or bosutinib 500 mg once daily. Patients intolerant to their most recent TKI were eligible for the study if they had a BCR-ABL1IS level higher than 0.1% at screening.
The cutoff date for this analysis was January 6, 2021. Treatment is ongoing in 56.7% of patients receiving asciminib and 22.4% of patients receiving bosutinib. The most common reason for treatment discontinuation was lack of efficacy in 37 (23.6%) and 27 (35.5%) patients, respectively.
At week 48, the MMR rate was 29.3% in patients who received asciminib and 13.2% with bosutinib, corresponding to a treatment difference of 16.1% after adjusting for major cytogenetic response status at baseline. Among patients with BCR-ABL1ISless than or equal to 1%, the response rate was 42.3% and 19.4% with asciminib and bosutinib, respectively.
By week 48, the cumulative incidence of MMR was 33.2% with asciminib and 18.6% with bosutinib, demonstrating that the efficacy benefit with asciminib was maintained with longer follow-up. In addition, deep molecular response rates continued to be higher with asciminib than bosutinib after longer follow-up.
The median duration of exposure was 15.4 months (range, 0.0-37.3 months) for asciminib and 6.8 months (range, 0.2-34.3 months) for bosutinib.
Despite a longer duration of exposure, the safety and tolerability profile of asciminib was consistent with that of the primary analysis, with fewer grade 3 or higher AEs with asciminib (54.5%) than bosutinib (67.1%).
The most common all-grade AEs leading to treatment discontinuation were thrombocytopenia (3.2%) and neutropenia (2.6%) with asciminib and increased alanine aminotransferase (5.3%) and neutropenia (3.9%) with bosutinib.
“Updated efficacy and safety results in ASCEMBL continue to support the use of asciminib as a new treatment option in CML, with the potential to transform standard of care in later-line CML,” Dr Mauro concluded.
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
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Mauro MJ, Minami Y, Rea D, et al. Efficacy and safety results from Ascembl, a multicenter, open-label, phase 3 study of asciminib, a rirst-in-class STAMP inhibitor, vs bosutinib in patients with chronic myeloid leukemia in chronic phase after ≥2 prior tyrosine kinase inhibitors: update after 48 weeks. Presented at ASH 2021; December 11-14, 2021. Abstract 310.