Adagrasib (Krazati)

Mechanism of action

From the NCI Drug Dictionary: An orally available, small molecule inhibitor that targets the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon oral administration adagrasib covalently binds to cytosine 12 within the switch II pocket of GDP-bound KRAS G12C, thereby inhibiting mutant KRAS-dependent signaling.

• IUPHAR/BPS

Diseases for which it is used

• Colorectal cancer, KRAS-mutated
• Non-small cell lung cancer, KRAS-mutated

History of changes in FDA indication

• 2022-12-12: Granted accelerated approval for adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. (Based on KRYSTAL-1_NSCLC)

History of changes in EMA indication

• 2023-11-09: CHMP recommendation for conditional marketing authorisation - KRAZATI as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and disease progression after at least one prior systemic therapy.

Also known as

• Code name: MRTX-849
• Brand name: Krazati