Aceminib/Asnib is beneficial for post-TKI CML-CP

According to research results published in 2025, Asciminib/Asciminib reacted with polymers at 24 weeks It is associated with response rates and is well tolerated in most adult patients with chronic phase chronic myeloid leukemia (CML-CP), a tyrosine kinase inhibitor (TKI).

Researchers report updated safety and efficacy results from an interim analysis of the phase 2, single-arm, open-label ASC2ESCALATE (NCT05384587) trial in patients with CML-CP who received 1 TKI (2L), with dose escalation for those with poor response. The study enrolled adults with 1L or 2L CML-CP but without the T315I mutation. The 1L cohort was not included in this interim analysis. Patients in the 2L cohort discontinued previous TKI due to ELN2020 warning or failure or intolerance to BCR: ABL1IS >0.1% at screening. Participants received Asnib 80 mg once daily (QD). If BCR::ABL1IS is >1% at Week 24, the dose is increased to 200 mg QD. At week 48, the dose is increased from 80 mg to 200 mg once daily or from 200 mg to 200 mg twice daily if BCR:ABL1IS >0.1%, otherwise patients can discontinue the study. Those patients with grade 3/4 or sustained grade 2 toxicity refractory to optimal management were not eligible for a dose increase at weeks 24 and/or 48 and continued to receive the same dose.

The current analysis includes101 pts with 2L CML-CP who received ≥1 doseof asinib at the cutoff of November 15, 2024. Their median age was 50 years old, and 57% were male. Their previous treatment included dasatinib (44.6%), imatinib (42.6%), nilotinib (9.9%), or bosutinib (5.0%), and 66.3% of the cohort had received ≥12 months of treatment. Previous treatment was discontinued due to ineffectiveness (56.4%) or intolerance (43.6%). As of the cutoff date, a total of 92 participants (91.1%) were currently receiving astanib and 9 patients (8.9%) had discontinued astanib, mostly due to adverse events (AEs; n=4) and patient decision-making (n=3).

AsnibThe median duration of exposure was26.1 weeks (range 6-100 weeks). Participants eligible for the efficacy analysis completed the assessment at their respective time points or terminated the assessment early (week 4, n=94; week 12, n=86; week 24, n=63). Among these patients, 46.8%, 84.9%, and 82.5% had BCR:ABL1IS ≤1% at weeks 4, 12, and 24, respectively. Deeper responses were observed at weeks 12 (major molecular response [MMR], 39.5%; molecular response [MR]4, 11.6%; MR4.5, 2.3%) and week 24 (MMR, 44.4%; MR4, 25.4%; MR4.5, 9.5%). Seven patients did not reach response milestones at weeks 24 (n=3) and 48 (n=4), and the dose was increased from 80 mg to 200 mg once daily.

Adverse events of all grades occurred in 96 participants (95%). Headache (22.8%) and nausea (20.8%) were all-grade adverse events occurring in ≥20% of patients. Grade ≥3 adverse events occurring in more than 5% of patients included hypertension (8.9%), thrombocytopenia (6.9%), and neutropenia (5.9%). Adverse events resulted in dose adjustment or treatment interruption in 27 participants (26.7%). Adverse events in four patients were also related to discontinuation of treatment, with one event occurring more than 30 days after the last dose of asinib. No arterial occlusive events or deaths during treatment were observed.

The researchers stated: These interim results further support asinib as a treatment option for 2L CML-CP.

Reference materials:https://www.hematologyadvisor.com/reports/chronic-myeloid-leukemia-cml-asciminib-beneficial-tki-treatment-risk/