Encouraging Phase 1 Analysis Findings for Asciminib Monotherapy in TKI-Resistant Chronic Phase CML

A phase 1 clinical trial has evaluated asciminib to treat chronic myeloid leukemia (CML) in the chronic phase without the BCR::ABL1^T315I mutation that has withstood two or more tyrosine kinase inhibitor (TKI) interventions. A final results analysis of this trial has yielded encouraging findings for long-term use of this agent for this condition and has been published in Leukemia.

“These results confirm the efficacy, safety and tolerability in these patients who had received multiple prior tyrosine kinase inhibitors,” wrote Jorge Cortes, MD, of Georgia Cancer Center at Augusta University, a coauthor of the analysis, in remarks forwarded to Blood Cancers Today.

The total cohort for the open-label, nonrandomized trial included 115 patients with chronic phase CML without the BCR::ABL1^T315I mutation. These patients received monotherapy with asciminib, a BCR::ABL1 inhibitor—either 10 to 200 mg twice daily or 80 to 200 mg once daily. The median duration of treatment was 5.9 years, and the longest duration was 8.4 years.

Fifty-six patients achieved a major molecular response, and in 50 patients, this response was maintained by trial cutoff. In the investigators’ Kaplan-Meier calculations, the estimated probability of patients maintaining response for at least 432 weeks, or approximately 8.3 years, was 88%.

“Considering that more than two thirds of patients had received at least 3 prior inhibitors, these response rates are unprecedented,” Dr. Cortes mentioned.

Regarding safety results in the total cohort, 76.5% of patients experienced adverse events (AEs) of grade 3 or worse severity. First-ever AEs, especially hematologic AEs, usually occurred within the first year of treatment.

“Nearly three fourths of the patients had received asciminib for more than three years, and the safety profile is unchanged, with few patients developing adverse events in later years,” Dr. Cortes elaborated.

In the total cohort, AEs led to treatment discontinuation for 13.0% of patients, dose adjustment or treatment interruption for 64.3%, and additional therapy for 92.2%. After completion of this trial, 60.9% of the patients continued to receive asciminib via post-trial access.

This trial identified no new safety signals for asciminib, and it determined the recommended dose of asciminib for an expansion cohort to be 40 mg twice daily.

“Since this study started in 2014, it provides very long-term safety evidence of asciminib. This drug has become a very valuable asset for treatment of patients, not only with resistance or intolerance to multiple therapies as per this report, but now also in earlier lines of therapy,” Dr. Cortes concluded.