Adagrasib, sold under the brand name Krazati, is an anticancer medication used to treat non-small cell lung cancer.
Adagrasib is an inhibitor of the RAS GTPase family.
It is taken by mouth.
The most common adverse reactions include diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation.
The most common laboratory abnormalities include decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.
Adagrasib is indicated for the treatment of adults 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.
KRYSTAL-1, a multicenter, single-arm, open-label clinical trial which included participants with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations.
Efficacy was evaluated in 112 participants whose disease has progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor, given either concurrently or sequentially.
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.