Need To Know

  • The phase 2 ASC2ESCALATE trial — which evaluates a response-guided dose optimization strategy for Asciminib in patients with chronic-phase chronic myeloid leukemia (CML-CP)–is unlike traditional fixed-dose approaches, as it begins patients on asciminib 80 mg once daily—the current FDA-approved starting dose—and prospectively escalates therapy for those who do not achieve optimal molecular milestones.
  • Dr. David J. Andorsky— a medical oncologist at  Rocky Mountain Cancer Centers and hematologist who co-authored the ASC2ESCALATE study–views the ASC2ESCALATE data as compelling evidence that a response-guided, dose-escalation strategy with asciminib can safely deepen molecular responses while maintaining excellent tolerability in patients with chronic-phase CML.

In conversation with SurvivorNet, Sarah Cannon Research Institute’s Dr. David Andorsky–who presented data from the phase 2 ASC2ESCALATE trial at the 2025 ASCO Annual Meeting–expressed his views on the findings, saying they reinforce his opinion that asciminib’s response-adapted dosing strategy offers a practical and well-tolerated way to individualize therapy and improve early molecular outcomes in chronic-phase CML.

“The study has a somewhat unique design in that it takes patients and starts them on the 80 milligram daily dose, which is the current FDA-approved dose,” Dr. Andorsky says. “At 24 weeks and 48 weeks, patients are assessed for response. If they have a PCR greater than 1% at 24 weeks, the dose is escalated to 200 milligrams daily.”

This adaptive design reflects a growing emphasis in CML management on early molecular response as a predictor of long-term outcomes.

ASC2ESCALATE (2L CML-CP) — Key Highlights

  • Phase 2, single-arm study of asciminib (ASC) in CML-CP after 1 TKI (2L) with dose escalation for pts with suboptimal response; ASC is also being assessed in a separate newly diagnosed (1L) cohort

  • 101 patients enrolled; 91% remained on treatment at data cutoff

  • ASC demonstrated high molecular response rates at Week 24

“The other five TKIs that are available for first-line therapy are what are called ATP-binding competitive TKIs,” Dr. Andorsky says. “They bind to the ATP-binding site of the molecule and shut it down in that way. Asciminib is the first that binds to the ABL myristoyl pocket, which is a different location on the molecule and therefore may not be susceptible to the same resistance mutations that we see emerging for other TKIs.”

Data presented from the trial show that 82.5% of patients achieved BCR-ABL1 levels below 1% at 24 weeks, indicating a high rate of early molecular control. Importantly, tolerability was favorable, with only four patients discontinuing therapy due to adverse events—suggesting strong retention and manageable toxicity.

Together, these findings support asciminib as a well-tolerated, mechanistically distinct option that may play an expanding role in chronic CML management.