The FDA has approved sotorasib (Lumakras; Amgen) with panitumumab (Vectibix; Amgen) for adult patients with KRAS G12C–mutated metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.1
The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device to aid in identifying patients with CRC whose tumors harbor KRAS G12C mutations and who may be eligible for Lumakras with Vectibix.
The FDA’s decision was based on data from CodeBreaK 300 (NCT05198934), an open-label, controlled trial in patients with KRAS G12C–mutated metastatic CRC who had previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in which 160 patients were randomly assigned to receive either sotorasib 960 mg orally once daily and panitumumab 6 mg/kg intravenously (IV) every 2 weeks, sotorasib 240 mg orally once daily and panitumumab 6 mg/kg IV every 2 weeks, or investigator’s choice of standard of care (SOC) trifluridine/tipiracil or regorafenib.
Patients who received a combination of sotorasib (960 mg) and panitumumab averaged a median progression-free survival of 5.6 months, compared with 2 months for those receiving the investigator’s choice SOC. The risk of disease progression was reduced by 52% (hazard ratio, 0.48), and the results were statistically significant (P=.005).
In terms of tumor response, 26% of patients in the sotorasib 960 mg/panitumumab group experienced tumor shrinkage, compared with 0% in the SOC group. The median duration of this response was 4.4 months, with some patients experiencing benefits at >6 months.
The most common adverse reactions for sotorasib 960 mg/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. The most common grade 3/4 laboratory abnormalities in ≥2 patients were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.
Reference
- FDA. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. January 16, 2025. Accessed February 10, 2025. ww.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer