# LITESPARK-012

Source: https://onco.cc/trials/litespark-012/  
OnCo record `litespark-012` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding belzutifan to first-line lenvatinib-pembrolizumab did not deliver, a reminder that later-line success does not guarantee first-line benefit.

## Summary

LITESPARK-012, trial NCT04736706 sponsored by Merck and reported at ASCO GU 2026, found that adding belzutifan, or the CTLA-4 antibody quavonlimab, to first-line lenvatinib plus pembrolizumab in untreated advanced clear-cell renal cell carcinoma did not deliver, a reminder that later-line success does not guarantee first-line benefit. It randomised 1,688 patients across three arms, and neither investigational triplet met the dual primary endpoints of progression-free and overall survival at the pre-specified interim analysis announced on 21 April 2026, with hazard ratios not disclosed. OnCo links it to renal cell carcinoma, belzutifan, lenvatinib and pembrolizumab. Belzutifan's role is therefore later line and adjuvant, and why the phase 1b/2 KEYMAKER-U03 signal did not carry into phase 3 is the open question.

## Fields

- Kind: Trial
- Status: negative
- Last checked: 2026-09-07
- Tags: lesson:first-line-intensification
- Registry id: NCT04736706
- Phase: 3
- Setting: Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab)
- Sponsor: Merck
- Enrolled: 1854
- Result: Primary endpoint not met (ASCO GU 2026).
- Outcomes: Progression-free survival (BICR) and overall survival (dual primary): Pembrolizumab + lenvatinib + belzutifan vs Pembrolizumab/quavonlimab + lenvatinib vs Pembrolizumab + lenvatinib
- Replication: Consistent with COSMIC-313: adding a third agent to a first-line IO doublet has not improved outcomes in clear-cell RCC. The phase Ib/II KEYMAKER-U03 signal for the belzutifan triplet did not carry into phase 3.

## Sources

- ClinicalTrials.gov NCT04736706: https://clinicaltrials.gov/study/NCT04736706
- CURE report: https://www.curetoday.com/view/litespark-012-trial-falls-short-in-advanced-kidney-cancer

## Connected records

- cancers: [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Belzutifan](https://onco.cc/drugs/belzutifan/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)

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