Trial results for a Phase 3 study (NCT03937219) investigating nivolumab in combination with cabozantinib and ipilimumab for previously untreated advanced or metastatic renal cell carcinoma were posted on ClinicalTrials.gov on 2025-09-10. The trial demonstrated an improved duration of progression-free survival (PFS) with a Hazard Ratio of 0.73 (95% CI: 0.57 to 0.94) and a p-value of 0.0131 compared to nivolumab and ipilimumab with placebo.
Background
The study investigated a combination therapy for patients with previously untreated advanced or metastatic renal cell carcinoma (RCC) classified as intermediate- or poor-risk by IMDC criteria.
Trial design
The study (NCT03937219) was a multicenter, randomized, double-blinded, controlled Phase 3 trial. It enrolled 855 subjects with previously untreated advanced or metastatic renal cell carcinoma. Participants were randomized in a 1:1 ratio to receive either cabozantinib in combination with nivolumab and ipilimumab, or nivolumab and ipilimumab in combination with cabozantinib-matched placebo. The trial's primary focus included evaluating the duration of progression-free survival (PFS) and overall survival (OS).
Key results
The trial results showed differences in progression-free survival and overall survival between the treatment arms. For the outcome of "Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)":
- The median PFS for the Placebo + Nivolumab + Ipilimumab group was 11.30 months. The median PFS for the Cabozantinib + Nivolumab + Ipilimumab group was not provided in the summary data.
For the outcome of "Duration of Overall Survival (OS)":
- The median OS for the Cabozantinib + Nivolumab + Ipilimumab group was 41.86 months.
- The median OS for the Placebo + Nivolumab + Ipilimumab group was 41.99 months.
A key analysis using the Log Rank method for PFS showed a Hazard Ratio (HR) of 0.73 (95.0% Confidence Interval: 0.57 to 0.94) with a p-value of 0.0131.
What this means
The results suggest that adding cabozantinib to nivolumab and ipilimumab improves progression-free survival in patients with previously untreated advanced or metastatic renal cell carcinoma, as indicated by the statistically significant Hazard Ratio of 0.73 and p-value of 0.0131. While the median PFS for the experimental arm was not provided, the hazard ratio indicates a favorable outcome. The overall survival data showed very similar median durations between the two treatment arms, suggesting the PFS benefit did not translate into a significant OS difference at the time of this analysis. These findings provide important data for clinicians considering combination therapies for advanced RCC.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03937219, titled "Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma," were posted on 2025-09-10 on clinicaltrials.gov.