Oncology FDA APPROVAL ● FDA Approval

FDA Approves Krazati (adagrasib) for KRAS G12C-Mutated NSCLC and in Combination for Colorectal Cancer

FDA Published March 31, 2026 DOI ↗

Key Takeaway

Consider for KRAS G12C-mutated NSCLC post-systemic therapy and for CRC with cetuximab after specific chemotherapy.

The FDA has granted accelerated approval to Krazati (adagrasib) for two oncologic indications. First, it is approved as a single agent for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. Second, it is approved in combination with cetuximab for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC) who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

This approval provides a targeted therapeutic option for patients with these specific KRAS G12C mutations, a historically challenging oncogenic driver. The indications are based on objective response rate (ORR) and duration of response (DOR), and continued approval is contingent upon verification of clinical benefit in confirmatory trials.

For patient selection, the presence of the KRAS G12C mutation must be confirmed using an FDA-approved test. For NSCLC, testing can be performed on plasma or tumor specimens, with tumor tissue testing recommended if plasma is negative. For CRC, testing is specified for tumor specimens.

＋ Clinical Details (Mechanism · Dosing · Trial Data · Warnings)

Mechanism of Action

Not reported in label.

Indication & Patient Population

KRAZATI is indicated as a single agent for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. KRAZATI in combination with cetuximab is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. Both indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

Dosing & Administration

The recommended dosage of KRAZATI as a single agent or in combination with cetuximab is 600 mg orally twice daily until disease progression or unacceptable toxicity. Tablets should be swallowed whole with or without food. If a dose is missed by more than 4 hours, it should be skipped and dosing resumed at the next scheduled time. If vomiting occurs after a dose, do not take an additional dose. For adverse reactions, a maximum of two dose reductions are permitted: first to 400 mg twice daily, then to 600 mg once daily. Permanently discontinue if unable to tolerate 600 mg once daily. When used with cetuximab, withhold or discontinue cetuximab when KRAZATI is withheld or discontinued, but KRAZATI may continue if cetuximab is permanently stopped.

Key Clinical Trial Data

Trial data not available in label.

Warnings & Contraindications

Not reported in label.

Place in Therapy

KRAZATI is a single-agent option for previously treated, KRAS G12C-mutated advanced NSCLC. For CRC, it is indicated specifically in combination with cetuximab for patients who have progressed on fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. Its accelerated approval status indicates that its use is based on surrogate endpoints, with confirmatory trials required to verify clinical benefit.

View Original Abstract ↓

1 INDICATIONS AND USAGE KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. ( 1.1 ) Colorectal cancer (CRC)* • In combination with cetuximab, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. ( 1.2 ) *These indications are approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of a clinical benefit in confirmatory trials. ( 1.1 , 1.2 ) 1.1 KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer KRAZATI, as a single-agent, is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test [see Dosage and Administration (2.1) ] , who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR) [see Clinical Studies (14.1) ]. Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial. 1.2 KRAS G12C-Mutated Locally Advanced or Metastatic Colorectal Cancer KRAZATI in combination with cetuximab is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test [see Dosage and Administration (2.1) ] , who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on ORR and DOR [see Clinical Studies (14.2) ] . Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial.