Table 1.
| Agent | AMG-510 (sotorasib) | MRTX849 (adagrasib) |
|---|---|---|
| Company | Amgen | Mirati therapeutics Inc |
| FDA approval date | May 18, 2021 | December 12, 2022 |
| Type of inhibitor | Irreversible covalent inhibitor of KRASG12C | Irreversible covalent inhibitor of KRASG12C |
| Mechanism of inhibition | Forms water bridges between the tyrosine residue found in the KRASG12C protein and the carboxyl group in sotorasib | Uses hydrogen mediated bonding of the hydroxyl group on the KRASG12C pocket with adagrasib’s pyrimidine ring |
| Number of NSCLC patients in phase I/II trial | N = 124 (NCT03600883) | N = 116 (NCT03785249) |
| Prior platinum-based chemotherapy and immunotherapy |
Platinum based chemotherapy only: 11 (8.7%) Both therapies: 102 (81.0%) |
Platinum based chemotherapy only: 2 (1.7%) Both therapies: 114 (98.3%) |
| Recommended starting dose based on phase I/II trial data | 960 mg once daily | 600 mg twice daily |
| Half-life | 5.5 h | 24.0 h |
| Cmax of steady state (µg/ml) | 7.5 | 3.25 |
| Objective response rate (ORR) | 37.1% | 42.9% |
| Disease control rate (DCR) | 80.6% | 96% |
| Progression-free survival (PFS) | 6.8 months (5.6 months in phase III) | 6.5 months |
| Overall survival rate | 12.5 months (10.6 months in phase III) | 12.6 months |
| TRAEs occurring in > 5% of patients, all grades | Gastrointestinal toxicities, nausea, vomiting, elevated alanine transaminase (ALT) and aspartate aminotransferase (AST) | Gastrointestinal toxicities including nausea, vomiting, diarrhea; fatigue, increased AST and ALT, EKG QTc prolongation |
| Grade 3+ TRAEs in phase II trial | 20.6% | 45% |
| TRAEs leading to discontinuation | 7.1% | 6.9% |
| Preclinical data indicating ability to penetrate the brain and cerebrospinal fluid | n/a | Presence of adagrasib detected in brain and cerebrospinal fluid |