ASC2ESCALATE Clinical Trial in CML: Asciminib Dose Escalation Strategy
David Andorsky, MD, discusses the dose escalation design of the ASC2ESCALATE study exploring asciminib's role in chronic myeloid leukemia.
The ASC2ESCALATE trial (NCT05384587) is a single-arm study investigating asciminib (Scemblix) in both the first-line and second-line treatment of chronic myeloid leukemia (CML). In an interview with Targeted OncologyTM, David Andorsky, MD, oncologist at SCRI at Rocky Mountain Cancer Centers, The US Oncology Network, discussed the methodology of the study, including its unique dose escalation strategy.
This second-line cohort, data from which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, included patients who had previously received 1 tyrosine kinase inhibitor (TKI) but were either experiencing suboptimal response, either not meeting major molecular response-level treatment milestones or encountering intolerable adverse effects, as determined by the investigator. This trial has a built-in dose escalation strategy, featuring 2 evaluation points at 6 and 12 months.
At the 6-month mark, if a patient's PCR level has not reached less than 1%, the asciminib dose is escalated from the standard FDA-approved 80 mg daily to 200 mg daily. A second escalation point is at 12 months, allowing for either a first-time or a second dose increase if the patient's PCR has not reached less than 0.1%, signaling a major molecular response.
For this interim analysis, investigators evaluated 101 patients for safety who had received at least 1 dose of asciminib. Among these, 63 patients had reached the initial 24-week (6-month) efficacy evaluation. Of those 63 patients, 7 underwent dose escalation. Investigators considered the data for these escalated patients somewhat immature, so it was not included in the ASCO presentation.
Investigators aim to provide more follow-up time to thoroughly assess whether this escalation strategy effectively allows patients with a suboptimal response to continue on the same medication at a higher dose and to understand the broader implications of this approach.
