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Adagrasib in the treatment of colorectal cancer

Sara F Haddad1, Youssef Bouferraa2, Kanika G Nair2

  • 1Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA.

Future Oncology (London, England)
|July 7, 2025
PubMed

Insights

Adagrasib, a KRAS G12C inhibitor, shows efficacy in metastatic colorectal cancer. Combination with cetuximab improved outcomes, leading to FDA approval.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • KRAS G12C mutations are present in 3-4% of metastatic colorectal cancer (mCRC) cases, associated with poor prognosis.
  • Adagrasib is an oral, selective, irreversible inhibitor of KRAS G12C.

Purpose of the Study:

  • To evaluate the efficacy and safety of adagrasib, both as monotherapy and in combination with cetuximab, in patients with KRAS G12C-mutated mCRC.

Main Methods:

  • Phase I/Ib KRYSTAL-1 study.
  • Established 600 mg twice daily as the recommended Phase II dose for adagrasib.
  • Assessed efficacy (ORR, OS) and safety of adagrasib +/- cetuximab.

Main Results:

  • Adagrasib monotherapy demonstrated efficacy in heavily pretreated mCRC patients.
  • Combination therapy with adagrasib and cetuximab achieved an ORR of 34% and a median OS of 15.9 months.
  • Adagrasib was well-tolerated in both monotherapy and combination settings.

Conclusions:

  • Adagrasib represents a novel and well-tolerated treatment option for KRAS G12C-mutated mCRC.
  • The combination of adagrasib and cetuximab offers improved efficacy and has received accelerated FDA approval.
Keywords:
KRAS inhibitorKRASG12CKrazatiMetastatic colorectal canceradagrasibsmall molecule inhibitor

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