|The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Asciminib, a first-in-class STAMP inhibitor, may be a new treatment option for patients with chronic myeloid leukemia in the chronic phase (CML-CP), according to the results from the ASCEMBL trial presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
Andreas Hochhaus, MD, of Klinik für Innere Medizin II, Jena, Germany, presented data indicating that asciminib significantly improved the rate of major molecular response (MMR) at 24 weeks compared with bosutinib, meeting the study’s primary objective.
“The ASCEMBL data support the use of asciminib as a new treatment option in CML, particularly in patients with resistance or intolerance to at least 2 TKIs,” Dr Hochhaus said. “BCR-ABL1 remains the key driver of CML even in patients beyond second line. Asciminib, as a specific BCR-ABL1 inhibitor, has demonstrated a favorable benefit-risk profile in this patient population by its unique ability to specifically target the ABL1 myristoyl pocket.”
The trial 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.
Treatment is ongoing in 61.8% of patients assigned to receive asciminib and 30.3% of patients assigned to get bosutinib. The most common reason for discontinuation across both arms was lack of efficacy and adverse events, which were both less frequent in the asciminib arm, Dr Hochhaus reported. Twenty-four patients assigned to bosutinib who experienced lack of efficacy switched to asciminib.
The median duration of follow-up was 14.9 months. The MMR rate at 24 weeks was 25.5% with asciminib and 13.2% with bosutinib. Common treatment difference after adjusting for MCyR status at baseline was 12.2%, which was statistically significant (95% CI, 2.19-22.3; 2-sided P =.029).
The advantage of asciminib was seen across most major demographic and prognostic subgroups, including patients who had 3 or more prior TKIs.
The probably of achieving MMR by 24 weeks was 25% for asciminib compared with 11.9% for bosutinib. The rate of complete cytogenetic response at 24 weeks was 40.8% with asciminib compared with 24.2% for bosutinib.
Additionally, more patients assigned to receive asciminib achieved deep molecular responses compared with patients who were administered bosutinib.
Grade 3 or worse adverse events occurred in more than half of patients assigned to asciminib (50.6%) and bosutinib (60.5%); however, the proportion of patients that discontinued treatment due to adverse events was lower with asciminib compared with bosutinib (5.8% vs 21.1%).
Two patients assigned asciminib and 1 patient assigned bosutinib had on-treatment deaths. Two patients randomly selected to receive asciminib died during survival follow-up due to CML.
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.
Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.
Hochhaus A, Boquimpani C, Rea D, et al. Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib (bos) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors (TKIs). Presented at 62nd ASH Annual Meeting & Exposition. Dec. 5-8, 2020. Abstract LBA-4.