Asciminib appeared to have clinical activity in a population of heavily pretreated patients with chronic myeloid leukemia (CML) who had developed resistance or unacceptable toxicity during treatment from tyrosine kinase inhibitors (TKIs), according to the results of a phase 1 dose-escalation study ( Identifier: NCT02081378). The findings were published in the New England Journal of Medicine.

The trial enrolled 150 patients, of whom 141 had chronic-phase and 9 had accelerated-phase CML. Eligible patients were those who developed resistance to or unacceptable toxicity from prior treatment with at least 2 TKIs. All patients received asciminib monotherapy between May 2014 and September 2017. 

Asciminib was given once or twice per day. Patients on a once-daily schedule had 3 possible dose levels (ie, 80 mg [18 patients], 120 mg [22 patients], and 200 mg [12 patients]) and patients on a twice-daily schedule had 7 possible dose levels (ie, 10 mg [1 patient], 20 mg [14 patients], 40 mg [35 patients], 80 mg [12 patients], 150 mg [13 patients], 160 mg [7 patients], and 200 mg [16 patients]).

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The trial population was heavily pretreated, with most patients (70%) having received at least 3 prior TKIs.

All patients had an adverse event of any grade, and 60% had a grade 3/4 adverse event. The most common grade 3/4 adverse events were increased lipase levels (10%), thrombocytopenia (9.3%), and hypertension (9.3%). A total of 5 dose-limiting toxicities occurred for the twice-daily schedule and 3 for the once-daily schedule. A maximum tolerated dose was not identified. 

A complete hematologic response rate of 92% (34 of 37 patients) was seen among patients with chronic-phase CML without a T315I mutation at study entry.

Overall, nearly half (48%) of evaluable patients with chronic-phase CML had or maintained a major molecular response by 12 months, which included patients who had developed resistance or unacceptable toxicity during ponatinib treatment. Among the 18 patients with chronic-phase CML who had with a T315I mutation at baseline, 5 (28%) achieved or maintained a major molecular response by 12 months. 

The study authors described the clinical activity seen with asciminib as “durable.”

Disclosure: The study was supported Novartis Pharmaceuticals. Some of the authors disclosed financial ties with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the original study.


  1. Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381(24):2315-2326.