# Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)

Source: https://onco.cc/pairings/lenvatinib-plus-pembrolizumab/  
OnCo record `lenvatinib-plus-pembrolizumab` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An anti-angiogenic pill makes immunotherapy work in endometrial cancers that would otherwise ignore it, at the cost of significant side effects.

## Summary

Lenvatinib plus pembrolizumab is a combination pairing for mismatch repair-proficient endometrial cancer that has progressed after platinum chemotherapy. VEGFR inhibition by lenvatinib reduces immunosuppressive myeloid cells and normalises tumour vessels so that T cells can enter, turning a cancer that largely ignores PD-1 monotherapy into one that responds. In the phase 3 KEYNOTE-775 / Study 309 trial the combination improved overall survival compared with chemotherapy both in all comers and in the pMMR population, but dose reductions and discontinuations for toxicity were common. In the first-line setting LEAP-001 failed to beat chemotherapy, so the pairing lives in the second line. It is one instance of the broader pattern of PD-1 blockade plus VEGF inhibition.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Lenvatinib + Pembrolizumab
- Type: combination
- Rationale: VEGFR inhibition reduces immunosuppressive myeloid cells and normalises vessels for T-cell entry; the combination overcame PD-1 monotherapy's ~13% response rate in pMMR disease.
- Evidence: Phase 3 OS benefit (second line); negative first-line trial.

## Sources

- ClinicalTrials.gov NCT03517449: KEYNOTE-775 / Study 309: https://clinicaltrials.gov/study/NCT03517449

## Connected records

- pairings: [PD-1 blockade + VEGF inhibition](https://onco.cc/pairings/io-plus-vegf/)
- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- trials: [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/)
- drugs: [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)

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