KRAS G12V se presenta en ~3–5% de NSCLC (menos común que G12C ~13% y G12D ~5%). A diferencia de KRAS...
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| ID | BMA-KRAS-G12V-NSCLC |
|---|---|
| Tipo | Relevancia terapéutica |
| Situación | reviewed 2026-05-03 | pending_clinical_signoff | actionability review required |
| Enfermedades | DIS-NSCLC |
| Fuentes | SRC-CIVIC SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Hechos relativos a la posibilidad de adoptar medidas
| Biomarcador | BIO-KRAS-G12V |
|---|---|
| Variante | KRAS G12V (p.G12V; c.35G>T) — sustitución de glicina a valina; sin cisteína para la unión covalente del inhibidor G12C |
| Enfermedad | DIS-NSCLC |
| El nivel de ESCAT | IV |
| Combinaciones recomendadas | Standard platinum-based chemoimmunotherapy per PD-L1 status (pembrolizumab ± carboplatin/paclitaxel or pemetrexed per KEYNOTE-189/024), Enrollment in KRAS G12V-selective inhibitor trials where available (e.g., RMC-6236 expansion cohorts) |
| Monoterapia contraindicada | Sotorasib (G12C-specific covalent — not active on G12V; structure lacks cysteine target), Adagrasib (G12C-specific covalent — same reason; G12V not a clinical indication), Anti-EGFR therapy (cetuximab/panitumumab) — not used in NSCLC regardless of KRAS status; relevant only in CRC |
| Resumen de las pruebas | KRAS G12V occurs in ~3–5% of NSCLC (less common than G12C ~13% and G12D ~5%). Unlike KRAS G12C, there is no FDA/EMA-approved selective inhibitor for G12V as of 2026 — the G12C-selective covalent inhibitors (sotorasib, adagrasib) require the cysteine substitution and are inactive against G12V. Standard treatment follows usual NSCLC algorithm: platinum-based chemotherapy + pembrolizumab (PD-L1 ≥50%) or chemoimmunotherapy (PD-L1 any) per NCCN/ESMO. Investigational strategies: pan-KRAS inhibitors (RMC-6236, Revolution Medicines — phase I/II KRYSTAL-G12V-like programs), KRAS G12V-selective non-covalent inhibitors in early clinical development, SOS1 inhibitors + MEK inhibitors (combinatorial approaches to bypass KRAS G12V). Adoptive T-cell therapy targeting KRAS G12V neoantigen on HLA-A*11:01 (NCT03399448, MSK) — early phase with objective responses reported (Leidner et al. NEJM 2022 in one metastatic rectal case; NSCLC trials ongoing). STK11 and KEAP1 co-mutations (common in KRAS-mutant NSCLC) predict inferior ICI response and should be tested concurrently. |
Notas
ESCAT IV: no approved targeted therapy for KRAS G12V in NSCLC (as of 2026). The absence of a cysteine residue in the G12V substitution prevents covalent binding by G12C-selective inhibitors (sotorasib, adagrasib). Clinical priority: (1) confirm KRAS G12V by validated NGS; (2) co-test PD-L1, STK11, KEAP1, TMB; (3) treat per PD-L1 algorithm; (4) refer to KRAS G12V-specific trials. HLA-A*11:01 typing may be relevant if adoptive T-cell therapy trials are available locally. KRAS G12V occurs at higher frequency in never-smokers compared with G12C (smoker-associated). Do not confuse with KRAS G12C — the mutation subtype must be confirmed before counseling patients about targeted therapy options; patients may have heard of sotorasib/adagrasib from community oncologists.
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