| Abstract: |
Asciminib targets the BCR::ABL1 myristoyl pocket, maintaining activity against BCR::ABL1T315I, which is resistant to most approved adenosine triphosphate–competitive tyrosine kinase inhibitors. We report updated phase I results (NCT02081378) assessing safety/tolerability and antileukemic activity of asciminib monotherapy 200 mg twice daily in 48 heavily pretreated patients with T315I-mutated chronic-phase chronic myeloid leukemia (CML-CP; data cutoff: January 6, 2021). With 2 years’ median exposure, 56.3% of patients continued receiving asciminib. Overall, 62.2% of evaluable patients achieved BCR::ABL1 ≤1% on the International Scale (IS); 47.6% and 81.3% of ponatinib-pretreated and -naive patients, respectively, achieved BCR::ABL1IS ≤1%. Of 45 evaluable patients, 48.9% achieved a major molecular response (MMR, BCR::ABL1IS ≤0.1%), including 34.6% and 68.4% of ponatinib-pretreated and -naive patients, respectively. MMR was maintained until data cutoff in 19 of 22 patients who achieved it. The most common grade ≥3 adverse events (AEs) included increased lipase level (18.8%) and thrombocytopenia (14.6%). Five (10.4%) patients experienced AEs leading to discontinuation, including 2 who discontinued asciminib and died due to COVID-19; these were the only deaths reported. These results show asciminib’s effectiveness, including in almost 50% of ponatinib pretreated patients, and confirm its risk-benefit profile, supporting its use as a treatment option for T315I-mutated CML-CP. (Figure presented.) © The Author(s) 2024. |
| Keywords: |
adult; clinical article; aged; aged, 80 and over; middle aged; young adult; gene mutation; genetics; mutation; hydroxyurea; clinical trial; fatigue; diarrhea; drug efficacy; drug safety; drug withdrawal; monotherapy; antineoplastic agents; follow up; follow-up studies; antineoplastic agent; gene; imatinib; protein kinase inhibitor; nausea; thrombocytopenia; drug resistance; drug resistance, neoplasm; dasatinib; chronic myeloid leukemia; tyrosine kinase inhibitors; protein tyrosine kinase inhibitor; drug dose escalation; protein kinase inhibitors; pyrazole derivative; multicenter study; pyrazoles; single drug dose; pancytopenia; bcr abl protein; phase 1 clinical trial; drug therapy; nilotinib; drug tolerance; fusion proteins, bcr-abl; thrombocytosis; pharmacokinetics; triacylglycerol lipase; antileukemic activity; myeloid leukemia; molecular diagnosis; nicotinamide; leukemia, myeloid, chronic-phase; bosutinib; niacinamide; major molecular response; ponatinib; very elderly; humans; human; male; female; article; asciminib; abl1 gene; coronavirus disease 2019; t315i gene; bcr gene; radotinib
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