Table 1.
Acquired resistance mechanisms to KRASG12C inhibitors in the preclinical setting and clinical trial patients.
| Ref. | KRASG12C inhibitor | Case Number | Acquired secondary KRAS mutations | Acquired activating KRAS Mutations | KRASG12C Amplification | Acquired TRK/MAPK/PI3K | Squamous Cell Transformation |
|---|---|---|---|---|---|---|---|
| Preclinical setting | |||||||
| (43) | adagrasib | - | Y96D | ||||
| Q99L | |||||||
| R68S | |||||||
| A59S | |||||||
| (43) | sotorasib | - | Y96D | ||||
| R68M | |||||||
| A59T | |||||||
| A59S | |||||||
| (46) | sotorasib | - | MET amplification | ||||
| Clinical trial patients | |||||||
| (44) | adagrasib | 1 | Y96C | ||||
| 3 | H95D R68S | G12V G12W | BRAF V600E | ||||
| 7 | Yes | ||||||
| 9 | MET amplification | ||||||
| 10 | MET amplification | ||||||
| 11 | Yes | ||||||
| 12 | Yes | ||||||
| 13 | MAP2K1 E102_103del | ||||||
| 15 | RET M918T | ||||||
| 16 | PIK3CA H1047R | ||||||
| (29) | adagrasib | – | Y96D | G12V G13D | NRAS Q61L NRAS Q61R NRAS Q61K BRAF V600E MAP2K1 Q56P MAP2K1 E102_104del | ||