Asciminib is well-tolerated and shows promising clinical activity in patients with Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) with baseline BCR-ABL1 levels less than 1%, according to data presented at the virtual 2020 EHA Annual Congress.

“Asciminib is a novel, specific inhibitor of BCR-ABL1 that targets the myristoyl binding pocket. Its unique mechanism of action is expected to result in improved safety/tolerability compared with available ATP-binding TKIs,” explained Timothy Hughes, MD, South Australian Health and Medical Research Institute, University of Adelaide, Australia, and colleagues.

The ongoing phase 1 study enrolled adult patients with Ph+ chronic phase or accelerated phase CML, who were relapsed/refractory or intolerant to ≥2 TKIs. Patients were assigned to dose-escalation or dose-expansion cohorts evaluating asciminib alone or in combination with other therapies.

The analysis presented at the virtual 2020 EHA Congress included patients enrolled in the asciminib monotherapy cohorts with BCR-ABL1^IS ≤1%, regardless of the reason for TKI discontinuation. The cutoff date was August 30, 2019.

The aim of the study was to evaluate the safety and efficacy of asciminib monotherapy in this patient population. The analysis included 48 patients in 9 dose cohorts (20, 40, 80, 150, 160, and 200 mg twice daily; 80, 120, and 200 mg once daily).

Median duration of study treatment exposure was 161 weeks (range, 2-271). At data cutoff, 42 (87.5%) patients remained on treatment; 36 (75.0%) in major molecular response (MMR) or better.

Cumulative response rates continued to increase over time among those patients who did not achieve MMR, MR⁴, or MR^4.5 at baseline. Overall, 18 (75.0%) of 24 patients, 16 (42.1%) of 38 patients, and 18 (42.9%) patients achieved MMR, MR⁴, and MR^4.5, respectively.

Median time to MMR among responders was 30 days. All 18 patients who achieved MMR maintained this or better for ≥2 years, apart from 3 patients whose BCR-ABL1^IS fluctuated around 0.1% but who were still in MMR at 60 months.

Among the 6 patients who did not achieve MMR by the cutoff date, 1 had BCR-ABL1^IS >1%, and 5 had BCR-ABL1^IS between 0.1% and 1%. Among patients who achieved MR⁴ or MR^4.5, 9 (56.3%) of 16 patients and 10 (55.6%) of 18 patients, respectively, maintained the response for ≥2 years.

The most common grade 3-4 adverse events (AEs), occurring in >10% of patients were lipase increase (27.1%) and hypertension (12.5%). Serious AEs were reported in 16 (33.3%) pf 48 patients, the most common myocardial infarction (n = 2; 4.2%).

“In conclusion, asciminib monotherapy was well-tolerated and showed promising clinical activity in patients with baseline BCR-ABL1 levels less than 1%,” concluded Dr Hughes during his presentation.

“These results support further investigation of asciminib in patients who do not achieve optimal response at earlier time points,” he added.—Janelle Bradley

Hughes T, Mauro MJ, Kim DW, et al. Asciminib in Heavily Pretreated Patients (Pts) With Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Sensitive to Tyrosine Kinase Inhibitor (TKI) Therapy. Presented at: the Virtual 2020 EHA Annual Congress; June 11-21, 2020. Abstract S170.