High Responses in Second-Line Chronic-Phase CML

TOPLINE:

Asciminib, a first-in-class BCR–ABL1 TKI, showed high molecular response rates and was well tolerated in the first prospective trial of its kind evaluating the drug as a dose-escalated second-line therapy for patients with chronic-phase chronic myeloid leukemia (CML) who had suboptimal responses to earlier therapies.

METHODOLOGY:

• The interim analysis on the single-arm, open-label study, conducted at 85 trial sites in the US, included 101 patients with chronic-phase CML who discontinued a prior TKI due to intolerance or suboptimal responses.
• Patients were treated with at least one dose of asciminib 80 mg once daily.
• If BCR–ABL levels were above 1% at week 24, the dose was increased to 200 mg daily, and if BCR–ABL levels were above 0.1% at 48 weeks, the dose was increased from 80 to 200 mg daily, or from 200 mg daily to 200 mg twice daily, or patients could be taken off the study.
• Those with any grade 3 or 4 or persistent grade 2 toxicities that were refractory to optimal management were ineligible for dose escalations.
• Reasons for prior treatment discontinuation were due to a lack of efficacy in 56.4% and intolerance in 43.6% of patients.

TAKEAWAY:

• At week 24, a major molecular response was achieved by 44.4% of patients, with 25.4% achieving a deep molecular response (MR4 or better).
• In all, 11.1% of patients were given dose escalations upon failing to achieve response milestones.
• Among 101 patients receiving at least one dose, asciminib was well tolerated by most patients.
• Asciminib’s safety profile was that observed in previous studies, with no new or worsening safety findings observed.
• Grade 3 and higher adverse events (AEs) included hypertension (8.9 %), thrombocytopenia (6.9%), and neutropenia (5.9%).
• AEs overall led to dose adjustment or interruption in 26.7% of patients and discontinuation in four patients.

IN PRACTICE:

“Asciminib, in contrast with other FDA-approved TKIs, binds to the ABL myristoyl pocket, which may reduce off-target effects compared to the other competitive TKI’s,” said first author David Jacob Andorsky, MD, of the Rocky Mountain Cancer Centers, US Oncology Research, Boulder, Colorado.

“Results from ASC2ESCALATE, the first prospective trial of asciminib in second-line chronic-phase CML with dose escalation in patients not achieving response milestones, further support asciminib as a treatment option in second-line chronic-phase CML,” he said.

“The outcomes in patients with asciminib dose escalations continue to be explored, with analyses planned for future presentations,” Andorsky noted.

SOURCE:

The analysis was presented at the American Society of Clinical Oncology (ASCO) 2025 in Chicago.
 

DISCLOSURES:

This study was sponsored by Novartis Pharmaceuticals. Andorsky reported having relationships with AbbVie, AstraZeneca, Celgene, and Novartis.