Provisional list of mutations that might confer resistance to asciminib based on the currently available data
| Reference . | Type of study . | Mutations . |
|---|---|---|
| Wylie et al. (2017)7 | In vitro screen in KCL-22 CML cells cultured in increasing concentrations of asciminib and IC50 data in luciferase-transformed murine Ba/F3 cells expressing native BCR::ABL1 as compared with various BCR::ABL1 mutants | P223S; K294E; A337V; P465S; V468F; I502L |
| Qiang et al. (2017)28 | In vitro screen of asciminib-resistant CML cell lines cultured in increasing concentrations of asciminib | C464W; M244V/A337V |
| Eide et al. (2019)11 | In vitro cell-based accelerated mutagenesis screen and IC50 data in murine Ba/F3 cells expressing native BCR::ABL1 as compared with various BCR::ABL1 mutants | A344P; F359V; F359I; F359C; P465S; G671R (based on outgrowing mutants) T315L; T315M; T315I/G250E; T315I/Y253H; T315I/E255V; T315I/M351T; T315I/H386R; T315I/E453K; E255V/299L; V299L/F317L; F317L/F359V (based on IC50 data in a selected panel of single mutations and CMs of interest) |
| Hughes et al. (2019)29 | Clinical trial (phase 1, CP and AP) | G109D*; Y115N*; A337T; G463S; G463D*; P465S*; V468F; I502L |
| Mauro et al. (2023)30 | Clinical trial (phase 1; 4-year update of T315I-negative CP patients) | M244V; G463D; G463S; V468F; I502L |
| Hochhaus et al. (2023)31 | Clinical trial (phase 3 asciminib vs bosutinib [ASCEMBL]) | M244V; E355G; F359V; T315I; A337T; P465S |
| Cortes et al. (2020)32 (ASH meeting abstract) | Clinical trial (phase 1, T315I-positive patients) | F359I; T315I/F359I; A337T/F359V; T315I/M244V; T315I/M351T; T315I/E453Q |
| Reference . | Type of study . | Mutations . |
|---|---|---|
| Wylie et al. (2017)7 | In vitro screen in KCL-22 CML cells cultured in increasing concentrations of asciminib and IC50 data in luciferase-transformed murine Ba/F3 cells expressing native BCR::ABL1 as compared with various BCR::ABL1 mutants | P223S; K294E; A337V; P465S; V468F; I502L |
| Qiang et al. (2017)28 | In vitro screen of asciminib-resistant CML cell lines cultured in increasing concentrations of asciminib | C464W; M244V/A337V |
| Eide et al. (2019)11 | In vitro cell-based accelerated mutagenesis screen and IC50 data in murine Ba/F3 cells expressing native BCR::ABL1 as compared with various BCR::ABL1 mutants | A344P; F359V; F359I; F359C; P465S; G671R (based on outgrowing mutants) T315L; T315M; T315I/G250E; T315I/Y253H; T315I/E255V; T315I/M351T; T315I/H386R; T315I/E453K; E255V/299L; V299L/F317L; F317L/F359V (based on IC50 data in a selected panel of single mutations and CMs of interest) |
| Hughes et al. (2019)29 | Clinical trial (phase 1, CP and AP) | G109D*; Y115N*; A337T; G463S; G463D*; P465S*; V468F; I502L |
| Mauro et al. (2023)30 | Clinical trial (phase 1; 4-year update of T315I-negative CP patients) | M244V; G463D; G463S; V468F; I502L |
| Hochhaus et al. (2023)31 | Clinical trial (phase 3 asciminib vs bosutinib [ASCEMBL]) | M244V; E355G; F359V; T315I; A337T; P465S |
| Cortes et al. (2020)32 (ASH meeting abstract) | Clinical trial (phase 1, T315I-positive patients) | F359I; T315I/F359I; A337T/F359V; T315I/M244V; T315I/M351T; T315I/E453Q |
Mutations have either been recovered from in vitro studies where resistant cell lines were obtained using various strategies or identified as newly emerging mutations in patients enrolled in the clinical trials. Myristate-binding site mutations are highlighted in italic. The asterisk denotes mutations detected in patients with a variant frequency <10%, mostly in combination with other myristate-binding pocket or catalytic site mutations.