Sotorasib Combination Approved for KRAS G12C-mutant Colorectal Cancer
The FDA approved sotorasib and panitumumab for metastatic colorectal cancer with the KRAS G12C mutation.
The U.S. Food and Drug Administration (FDA) approved sotorasib (Lumakras) in combination with panitumumab (Vectibix) for the treatment of metastatic colorectal cancer that harbors the KRAS G12C mutation and has been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
The FDA also approved a companion diagnostic to determine KRAS status and eligibility in these patients.
Sotorasib is a targeted therapy that inhibits KRAS G12C, a mutated form of the KRAS protein that promotes tumor growth in many cancer types. This is the first colorectal cancer approval for sotorasib, which previously received accelerated approval to treat KRAS G12C-mutant lung cancers. Panitumumab is a targeted antibody that blocks the activity of the EGFR pathway, which can aid the growth and survival of tumors. Blocking EFGR may also help prevent tumors from becoming resistant to sotorasib.
This is the second approval of a combination approach targeting both KRAS G12C and EGFR for this colorectal cancer population.
This approval was based on results from the randomized, open-label, controlled phase III CodeBreaK 300 trial, in which 160 patients with metastatic colorectal cancer harboring KRAS G12C mutations were randomly assigned (1:1:1) to receive either: sotorasib (960 mg dose) and panitumumab, a lower dose of sotorasib (240 mg) and panitumumab, or investigator’s choice of standard-of-care therapy.
Among patients treated with 960 mg sotorasib and panitumumab, 26% experienced a treatment response, compared with 0% of those treated with the standard of care. Patients who received 960 mg sotorasib plus panitumumab also had a 52% lower risk of disease progression or death compared with those who received standard-of-care therapy. Half of the patients who received 960 mg sotorasib plus panitumumab survived at least 5.6 months before disease progression or death, compared with a median of 2 months for those who received the standard of care.
The recommended dose for sotorasib is 960 mg orally once a day, and the recommended dose for panitumumab is 6 mg/kg via intravenous infusion every two weeks until disease progression, unacceptable toxicity, or the discontinuation of sotorasib.
Colorectal cancer is a cancer that forms in the large intestine or rectum, and KRAS G12C mutations are found in approximately 3% to 4% of colorectal cancer cases. According to federal statistics, it was estimated that 152,810 individuals would be diagnosed with colorectal cancer and 53,010 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on January 16, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.
