Cabozantinib, Nivolumab, Ipilimumab Combination Does Not Reach PFS


Triplet combination demonstrates a reduction in the risk of disease progression or death in individuals with previously untreated advanced intermediate- or poor-risk renal cell carcinoma.

The combination of cabozantinib (Cabometyx; Exelixis Inc), nivolumab and ipilimumab has not reached the median progression-free survival (PFS) compared with the combination of nivolumab and ipilimumab in individuals with previously untreated advanced intermediate- or poor-risk renal cell carcinoma (RCC).

The data were presented during the Presidential Symposium 3 on September 12 at the European Society of Medical Oncology Congress.

“I look forward to presenting detailed results from COSMIC-313, which provide a clear look at the efficacy and safety profile for this combination of cabozantinib plus dual checkpoint inhibition,” Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, said in a statement.

“As the first trial with a control arm of nivolumab plus ipilimumab, COSMIC-313 was designed to answer an important question of whether adding cabozantinib to dual checkpoint inhibition can improve outcomes for this poor- and intermediate-risk [RCC] patient population,” she said. “I am pleased that the trial demonstrated a significant [PFS] benefit in patients receiving the triplet combination.”

Individuals in the trial had intermediate- or poor-risk advanced RCC according to the International Metastatic RCC Database Consortium with a clear-cell component and Karnowski performance status of 70% or greater. Approximately 75% of the 855 individuals were intermediate-risk, while the rest were poor-risk.

Previously, the triplet combination demonstrated a reduction in the risk of disease progression or death compared with the combination of nivolumab and ipilimumab, determined by a blinded independent radiology committee. Prespecified interim analysis for the secondary endpoint of overall survival (OS) showed that the triplet combination compared with the doublet combination did not demonstrate a significant benefit. The trial will continue for the next OS analysis.

The new results demonstrated that the median PFS was not reached for the triplet combination, but the doublet combination reached 11.3 months. Additionally, the objective response rates in the PFS intent-to-treat population were 43% and 36%, respectively.

The median duration of response was not reached in either treatment arm, and the PFS subgroup analyses was also presented at the conference.

Investigators observed that the safety profile was reflective of the known safety profiles for each single agent, as well as the combination regimens, and no new safety signals were seen.

Treatment-emergent adverse events (TEAE) of grade 3 or 4 occurred in 73 of individuals with the triplet combination and 41% of individuals treated with the doublet combination.

Approximately 1% of individuals in each arm had a grade 5 treatment-related adverse events, and approximately 12% of individuals in the triplet combination and 5% in the doublet combination discontinued treatment, because of TEAEs.

Cabozantinib is approved for the treatment of individuals with advanced RCC, individuals with advanced RCC as a first line treatment in combination with nivolumab, individuals with hepatocellular carcinoma who have been previously treated with sorafenib, and individuals aged 12 years or older with locally advanced or metastatic differentiated thyroid cancer that progressed following prior VEGFR-targeted therapy who are ineligible or radioactive iodine-refractory.


Exelixis announces detailed results from phase 3 COSMIC-313 pivotal trial in individuals with previously untreated advanced kidney cancer at ESMO 2022. News release. Business Wire. September 7, 2022. Accessed September 9, 2022.

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