# COSMIC-313

Source: https://onco.cc/trials/cosmic-313/  
OnCo record `cosmic-313` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first triplet trial in kidney cancer slowed progression but did not help patients live longer, and added toxicity.

## Summary

COSMIC-313, trial NCT03937219 sponsored by Exelixis and reported in 2022, was the first triplet trial in kidney cancer, and it slowed progression but did not help patients live longer while adding toxicity. It randomised 855 patients with untreated intermediate or poor-risk clear-cell renal cell carcinoma to cabozantinib plus nivolumab and ipilimumab or the doublet alone, met its primary progression-free survival endpoint, but showed no overall survival difference at the final analysis with far more severe adverse events, and poor-risk patients did not benefit even on progression; the triplet was not approved. OnCo links it to renal cell carcinoma, cabozantinib, nivolumab, ipilimumab and Sumanta K. Pal. Whether any third agent can add to an immunotherapy doublet is the open question.

## Fields

- Kind: Trial
- Status: mixed
- Last checked: 2026-09-07
- Tags: lesson:pfs-without-os
- Registry id: NCT03937219
- Phase: 3
- Setting: Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab
- Sponsor: Exelixis
- Enrolled: 855
- Result: PFS HR 0.73; OS HR 1.02 (no benefit).
- Outcomes: Progression-free survival: Cabozantinib + nivolumab + ipilimumab vs Nivolumab + ipilimumab, HR 0.73; Overall survival (final): Triplet 41.9 months vs Doublet 42 months, HR 1.02
- Replication: Consistent with LITESPARK-012: first-line triplets have not improved OS in RCC.

## Sources

- ClinicalTrials.gov NCT03937219: https://clinicaltrials.gov/study/NCT03937219

## Connected records

- cancers: [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Ipilimumab](https://onco.cc/drugs/ipilimumab/), [Nivolumab](https://onco.cc/drugs/nivolumab/)
- companies: [Exelixis](https://onco.cc/companies/exelixis/)
- people: [Sumanta K. Pal](https://onco.cc/people/sumanta-pal/)

---
JSON: https://onco.cc/api/v1/entities/cosmic-313.json