The combination of adagrasib (Krazati) and cetuximab (Erbitux) for the treatment of adult patients with KRAS G12C–mutant locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Phase 1/2 KRYSTAL-1 trial in which adagrasib plus cetuximab led to a confirmed overall response rate (ORR) of 34% consisting of all partial responses.
Patients were required to have locally advanced or metastatic KRAS G12C–mutated CRC following prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and a VEGF inhibitor, if eligible.
Patients received 600 mg of adagrasib twice daily plus cetuximab which was administered either biweekly at 500 mg/m2 every two weeks or weekly first at 400 mg/m2 followed by 250 mg/m2 weekly.
The most frequent adverse effects occurring in at least 20% of patients were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.
The recommended dose of adagrasib is 600 mg orally twice daily until disease progression or unacceptable toxicity.