The COSMIC-313 trial is a phase III clinical trial that investigated the efficacy and safety of combining cabozantinib with the immunotherapy drugs ipilimumab (IPI) and nivolumab (NIVO) in patients with previously untreated advanced clear-cell renal cell carcinoma (RCC). RCC is a type of kidney cancer that accounts for around 3% of all adult cancers.
The trial enrolled patients with advanced/metastatic RCC who were randomly assigned to receive either the combination of cabozantinib, IPI, and NIVO or the combination of placebo + IPI and NIVO. The primary endpoint of the trial was progression-free survival (PFS), which is the length of time a patient lives without their cancer getting worse.
The trial found that the combination of cabozantinib, IPI, and NIVO resulted in a statistically significant improvement in PFS compared to the combination of IPI and NIVO alone.
The PFS benefit was observed across all subgroups of patients, except for those in the International Metastatic RCC Database Consortium (IMDC) poor risk group. This group of patients did not experience a significant improvement in PFS with the addition of cabozantinib.
The trial also found that the combination of cabozantinib, IPI, and NIVO resulted in a higher overall response rate (ORR) compared to IPI/NIVO alone. The ORR was higher in the combination group compared to in the IPI/NIVO alone group.
In terms of safety, the combination of cabozantinib, IPI, and NIVO was generally well-tolerated, but it did result in a higher rate of treatment-related adverse events (TRAEs) compared to IPI/NIVO alone. The most common TRAEs included diarrhea, fatigue, and hepatotoxicity.
Overall, the COSMIC-313 trial demonstrated that the combination of cabozantinib, IPI, and NIVO was an effective treatment option for patients with advanced RCC, with a significant improvement in PFS and ORR.
However, the lack of benefit in the IMDC poor risk group warrants further investigation. Further follow up is also needed to study the overall survival data.
