Adagrasib is an oral targeted cancer therapy used primarily to treat adults with non-small cell lung cancer (NSCLC) and, in combination with cetuximab, certain types of colorectal cancer, both characterized by the KRAS G12C mutation.
Adagrasib is marketed under the brand name Krazati
Adagrasib is indicated for adults with KRAS G12C-mutated NSCLC that is locally advanced or metastatic, particularly in patients who have already received at least one systemic therapy.
It is also approved for use with cetuximab to treat KRAS G12C-mutated metastatic colorectal cancer in adults who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Adagrasib is a KRAS inhibitor that selectively and irreversibly binds to the mutant KRAS G12C protein, locking it in an inactive state.
This prevents aberrant signaling that drives unchecked cell division and tumor growth in cancers with this specific KRAS mutation, while sparing normal (wild-type) KRAS.
The typical recommended dose is 600 mg of adagrasib taken orally twice daily, continued until disease progression or unacceptable toxicity occurs.
The typical dosing schedule for adagrasib is 600 mg taken orally twice daily, continued until disease progression or unacceptable toxicity occurs. If severe side effects occur, the dose may be reduced first to 400 mg twice daily, and then to 600 mg once daily. If the lowest dose is not tolerated, treatment should be discontinued.
The most frequent adverse reactions (≥25%) include: Nausea, vomiting, diarrhea, and decreased appetite Fatigue and musculoskeletal pain Rash and dry skin Headache and cough Elevated liver enzymes (AST/ALT) Edema and anemia
Gastrointestinal side effects-nausea, vomiting, diarrhea, are very common and may require supportive care or dose adjustments in severe cases.
Some patients can experience hepatotoxicity.
Other possible side effects include decreased hemoglobin, low sodium or potassium, and rare but serious issues like interstitial lung disease or prolonged QT interval on ECG.