The Food and Drug Administration has approved sotorasib (Lumakras) in combination with panitumumab (Vectibix) for patients with colorectal cancer KRAS G12C mutations who have previously received chemotherapy. In addition, the FDA has approved the therascreen KRAS RGQ PCR Kit by QIAGEN GmbH as a companion diagnostic to identify eligible patients.
The approval is based on results from the CodeBreaK 300 clinical trial, a randomized, open-label study that evaluated the safety and efficacy of combining sotorasib with panitumumab. A total of 160 patients participated in the trial, all of whom had KRAS G12C-mutated metastatic colorectal cancer. Participants were randomly assigned to one of three treatment groups: one receiving sotorasib at 960 mg daily combined with panitumumab at 6 mg/kg every 2 weeks, another receiving a lower dose of sotorasib at 240 mg daily combined with panitumumab, and a third group receiving standard care with either trifluridine/tipiracil or regorafenib
The primary outcome measured was progression-free survival, assessed by blinded independent central review using RECIST v1.1 criteria. Patients receiving the higher-dose combination of sotorasib and panitumumab experienced a median progression-free survival of 5.6 months compared to 2 months in the standard care group. This represented a statistically significant improvement.
Although overall survival was also evaluated, the final analysis did not achieve statistical significance. The overall response rate for the higher-dose combination therapy was 26%, compared to zero in the standard care group. The median duration of response was 4.4 months for patients in the combination therapy group. In contrast, the lower-dose combination of sotorasib and panitumumab did not show a statistically significant improvement in progression-free survival compared to standard care.
The most common side effects reported in the sotorasib and panitumumab combination group were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Laboratory tests revealed decreases in magnesium, potassium, and calcium levels among some patients.
The recommended dosing for sotorasib is 960 mg orally once daily, while panitumumab is administered intravenously at a dose of 6 mg/kg every 2 weeks. The first dose of sotorasib should be given before the initial panitumumab infusion, and treatment should continue until the disease progresses or toxicity becomes unacceptable.