Secondary KIT mutations after imatinib failure cluster in exon 13/14 (ATP-binding pocket...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-KIT-EXON13-17-GIST |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-GIST |
| Sources | SRC-CIVIC SRC-NCCN-MELANOMA-2025 |
Actionability Facts
| Biomarker | BIO-KIT |
|---|---|
| Variant | exon 13/14 (ATP-binding) or exon 17/18 (activation loop) secondary mutation post-imatinib |
| Disease | DIS-GIST |
| ESCAT tier | IIA |
| Recommended combinations | sunitinib (2L; preferred for exon 13/14 ATP-binding secondaries), regorafenib (3L), ripretinib (4L+; broad activation-loop and ATP-binding coverage) |
| Contraindicated monotherapy | imatinib re-challenge alone (resistant by definition) |
| Evidence summary | Secondary KIT mutations after imatinib failure cluster in exon 13/14 (ATP-binding pocket — V654A, T670I) or exon 17/18 (activation loop — D816, D820, N822, Y823). Sunitinib (Demetri Lancet 2006) covers exon 13/14 secondaries; regorafenib (GRID) provides 3L coverage; ripretinib (INVICTUS) is a switch-control inhibitor active across both classes — preferred 4L+. |
Notes
ESCAT IIA. OncoKB Level 1 (per OncoKB therapeutic levels for the approved sequenced TKI flow). Source-gap as DIS-GIST. ctDNA / repeat biopsy can guide TKI selection between sunitinib (ATP-binding) and ripretinib (activation-loop) when secondary genotype is known.
Used By
No reverse references found in the YAML corpus.