Class 2 BRAF (e.g., K601E, L597, fusions) — RAS-independent, signal as dimers. Class 3 BR...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-BRAF-CLASS3-NSCLC |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-NSCLC |
| Sources | SRC-CIVIC SRC-NCCN-NSCLC-2025 |
Actionability Facts
| Biomarker | BIO-BRAF-V600E |
|---|---|
| Variant | non-V600 (Class 2 / Class 3 — kinase-dead, RAS-dependent) |
| Disease | DIS-NSCLC |
| ESCAT tier | IIIB |
| Recommended combinations | trametinib monotherapy (Class 2; investigational), clinical trial enrollment (pan-RAF + MEKi) |
| Contraindicated monotherapy | vemurafenib / dabrafenib monotherapy (paradoxical RAS-RAF activation), encorafenib monotherapy (same paradoxical effect) |
| Evidence summary | Class 2 BRAF (e.g., K601E, L597, fusions) — RAS-independent, signal as dimers. Class 3 BRAF (e.g., G466, N581, D594) — kinase-impaired, RAS-dependent. Neither responds well to V600E-targeted vemurafenib. Trametinib monotherapy or MEKi + pan-RAF inhibitors under investigation. NCI-MATCH subprotocol H (trametinib for non-V600 BRAF) showed limited responses. |
Notes
ESCAT IIIB / X. OncoKB Level 4 (biological evidence). Distinguish from V600E carefully: same gene, opposite drug strategy.
Used By
Actionability
BMA-BRAF-V600E-NSCLC- BRAF V600E in advanced NSCLC (≈1-2% of adenocarcinomas): dabrafenib + trametinib gives OR...