Table 1 Comparison of AMG-510 and MRTX849 [11, 15, 17, 24, 25, 39, 41,42,43, 46, 48,49,50, 52,53,54,55,56,57,58,59]

Company

Amgen

Mirati therapeutics Inc

FDA approval date

May 18, 2021

December 12, 2022

Type of inhibitor

Irreversible covalent inhibitor of KRAS^G12C

Irreversible covalent inhibitor of KRAS^G12C

Mechanism of inhibition

Forms water bridges between the tyrosine residue found in the KRAS^G12C protein and the carboxyl group in sotorasib

Uses hydrogen mediated bonding of the hydroxyl group on the KRAS^G12C 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

C_max 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