ASCEMBL study details
ASCEMBL is a phase 3 study in which patients with CML who had received at least two previous TKIs were randomized to asciminib (n = 157) 40 mg twice daily or bosutinib (n = 76) 500 mg once daily. In a protocol amendment, patients with documented failure on bosutinib were allowed to switch to asciminib.
The main reason for discontinuing the last TKI therapy was lack of efficacy in approximately two-thirds of patients. More patients in the asciminib than the bosutinib group received two prior lines of therapy (52% vs. 40%); the others had received three or more prior lines of therapy.
Median follow-up for the data cutoff was 14.9 months.
Dr. Hochhaus reported that treatment discontinuation was lower in patients receiving asciminib than bosutinib (38% vs. 70%) and was mostly due to lack of efficacy (21% vs. 32%) or adverse events (5% vs. 21%).
The study met its primary endpoint: major molecular response (MMR) was approximately twice as high with asciminib than bosutinib at 24 weeks (25.5% vs. 13.2%; P = .029). Treatment effect for MMR was 12.2%. Median duration of exposure to asciminib was 43.4 weeks for asciminib and 29.2 weeks for bosutinib.
“Consistent treatment effect was seen across all subgroups of patients, and MMR rates were consistently high for patients on asciminib across all prior lines of therapy,” Dr. Hochhaus reported.
The probability of achieving MMR at 24 weeks was higher for patients receiving asciminib (25% vs. 11.9%) and started at week 12, he noted. Complete cytogenetic response was also higher for patients receiving asciminib (40.8% vs. 24.2%).
The occurrence of grade 3 or higher adverse events was lower with asciminib than bosutinib (51% vs. 61%). Thrombocytopenia and neutropenia were more common with asciminib and gastrointestinal events were more common with bosutinib. Arterial occlusion events were reported in five patients receiving asciminib and one patient receiving bosutinib. Most of these patients had prior exposure to imatinib, nilotinib, and/or dasatinib.
Dr. Mauro, a coinvestigator of the phase 3 study, also treated patients with the drug in the phase 1 study. “I feel asciminib has proven to be very well tolerated, with rare to absent cases of intolerance,” he said. Cardiovascular and cardiopulmonary adverse events are exceedingly rare as well.
Longer follow-up of the ASCEMBL study and continued follow-up of the myriad of groups from the phase 1 trial (T315I-positive patients treated with higher-dose asciminib, combination therapy with imatinib/nilotinib/dasatinib plus asciminib, and others) will be essential to settle any questions regarding selective adverse events of interest such as vascular occlusion, Dr. Mauro noted.
Dr. Hochhaus has reported receiving research funding from Novartis, Incyte, Pfizer, and Bristol-Myers Squibb. Dr. Hobbs has reported serving on advisory boards for Novartis. Dr. Mauro has reported financial relationships with Bristol-Myers Squibb, Novartis, Takeda, Pfizer, and Sun Pharma/SPARC.
A version of this article first appeared on Medscape.com.