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FDA Grants Accelerated Approval to Adagrasib With Cetuximab for Patients With KRAS G12C-Mutated Colorectal Cancer
On June 21, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to adagrasib plus cetuximab for patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer, who had received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The mutation status must be determined by an FDA-approved test. This regulatory decision was based on the KRYSTAL-1 trial.
This phase 1/2 multicenter, single-arm, expansion cohort trial enrolled 94 patients in this population who received 600 mg adagrasib twice daily plus cetuximab, either 100 mg/m2 every 2 weeks or 250 mg/m2 weekly with a 400 mg/m2 loading dose. If patients discontinued adagrasib they had to also discontinue cetuximab, however cetuximab discontinuation did not require adagrasib discontinuation. The major efficacy outcome measurements of this trial were confirmed overall response rate (ORR) and duration of response (DOR) by blinded independent central review.
The ORR was 34% with all responses partial. The median DOR was 5.8 months, with 31% of patients achieving a DOR of at least 6 months. The most common adverse reactions, occurring in ≥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 for adagrasib is 600 mg twice daily until disease progression or unacceptable toxicity.
Source:
FDA grants accelerated approval to adagrasib with cetuximab for KRAS G12C-mutated colorectal cancer. Published online: June 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-cetuximab-kras-g12c-mutated-colorectal-cancer
