# CLEAR (KEYNOTE-581)

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

## TL;DR

The combination with the longest progression-free survival ever reported in first-line kidney cancer, at nearly two years.

## Summary

CLEAR, also KEYNOTE-581, trial NCT02811861 sponsored by Eisai and Merck and reported in 2021, produced the combination with the longest progression-free survival ever reported in first-line kidney cancer, at nearly two years. It randomised 1,069 patients with untreated advanced clear-cell renal cell carcinoma to lenvatinib plus pembrolizumab, lenvatinib plus everolimus or sunitinib, met its primary progression-free survival endpoint with a very large effect and a high response rate including many complete responses, and showed a survival benefit whose curves separated late, leading to FDA approval in August 2021, although the 20 mg lenvatinib dose drives high toxicity with dose reductions in about seventy percent. Whether a lower lenvatinib starting dose would keep the efficacy is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT02811861
- Phase: 3
- Setting: Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm)
- Sponsor: Eisai / Merck
- Enrolled: 1069
- Result: PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79.
- Outcomes: Progression-free survival: Lenvatinib + pembrolizumab 23.9 months vs Sunitinib 9.2 months, HR 0.39; Overall survival (final): Lenvatinib + pembrolizumab 53.7 months vs Sunitinib 54.3 months, HR 0.79
- Replication: Consistent with other IO-TKI doublets; lenvatinib-everolimus arm improved PFS but not OS versus sunitinib.

## Sources

- ClinicalTrials.gov NCT02811861: https://clinicaltrials.gov/study/NCT02811861

## 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: [Everolimus](https://onco.cc/drugs/everolimus/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sunitinib](https://onco.cc/drugs/sunitinib/)
- companies: [Eisai](https://onco.cc/companies/eisai/)
- people: [Robert J. Motzer](https://onco.cc/people/robert-motzer/)
- terms: [IMDC risk groups (favourable / intermediate / poor)](https://onco.cc/terms/imdc-risk/)

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