Chronic myeloid leukaemia (CML) carries a particularly poor prognosis following the failure of second line treatment, due to the limited number of treatment options thereafter. In recent years, tyrosine kinase inhibitors (TKIs) have increased the chances of survival. However, these too display dwindling levels of efficacy following successive lines of treatment in a progressive setting, due to a commonly-shared mechanism of action. Presented recently at ASH 2020, the phase III ASCEMBL trial has concluded that asciminib, a STAMP inhibitor, the first of its kind, is almost twice as effective, compared to the current standard-of-care (SoC), despite participants already having been exposed to two lines of TKIs.
The ASCEMBL trial evaluated asciminib (40mg twice daily), in comparison to bosutinib (500mg once daily), enrolling 233 patients with chronic phase-CML. Eligible participants had previously been treated with ≥2 TKIs. The primary endpoint of this study was major molecular response (MMR) at 24 weeks, with safety as a secondary endpoint. Treatment was continued until disease progression or unacceptable toxicity.
At 24 weeks, the MMR of patients who received asciminib was 25.5%, whilst patients who received bosutinib achieved an MMR of 13.2%. At the time of this analysis, complete cytogenetic response (CCyR) was also achieved in 40.8% of asciminib patients and 24.2% of bosutinib patients. This response also came about faster, with asciminib achieving a median time to MMR of 12.7 weeks, compared to 14.3 weeks with bosutinib. Median duration of exposure was 43.4 weeks and 29.2 weeks, respectively. Asciminib also presented a superior safety profile, with grade ≥3 adverse events occurring in 50.6% and 60.5% of pts receiving asciminib and bosutinib, respectively. Less patients receiving asciminib encountered treatment discontinuation (5.8% vs. 21.1%).
In the phase III ASCEMBL trial, asciminib demonstrated a superior efficacy to the current standard-of-care. Furthermore, positive clinical outcomes were produced at a quicker rate and with a longer median exposure, asciminib demonstrates a long-lasting efficacy that can improve the patient’s quality of life. Combined with the improved safety profile over the SoC, this data supports the use of asciminib in chronic-phase chronic myeloid leukaemia patients, who have already received ≥2 prior TKIs.
Hochhaus A, 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 Crhonic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs). Presented at ASH 2020; Abstract LBA-4.