# PD-1 blockade + VEGF inhibition

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

## TL;DR

Normalising the tumour's blood vessels lets immune cells in, and VEGF blockade removes an immunosuppressive signal.

## Summary

This combination pairs Immune checkpoint inhibitors with Anti-angiogenic therapy against VEGF. VEGF suppresses dendritic cell maturation, promotes Tregs and MDSCs and produces leaky vessels that block T-cell infiltration, so normalising the vessels lets immune cells in and removes an immunosuppressive signal, linking the VEGF angiogenesis and PD-1 / PD-L1 immune checkpoint pathways. It is standard in Renal cell carcinoma (pembrolizumab-axitinib, nivolumab-cabozantinib), Hepatocellular carcinoma (atezolizumab-bevacizumab) and Endometrial cancer (lenvatinib-pembrolizumab), on multiple phase 3 trials with overall survival benefit. Ivonescimab fuses both functions into one molecule and beat pembrolizumab in Non-small-cell lung cancer.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Immune checkpoint inhibitors + Anti-angiogenic therapy
- Type: combination
- Rationale: VEGF suppresses dendritic cell maturation, promotes Tregs and MDSCs, and produces leaky vessels that block T-cell infiltration.
- Evidence: Multiple phase 3 OS benefits; bispecific validation.

## Sources

- CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer (New England Journal of Medicine 2021): https://doi.org/10.1056/NEJMoa2035716
- ClinicalTrials.gov NCT05499390: HARMONi-2: https://clinicaltrials.gov/study/NCT05499390

## Connected records

- cancers: [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- drugs: [Atezolizumab](https://onco.cc/drugs/atezolizumab/), [Ivonescimab](https://onco.cc/drugs/ivonescimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- pairings: [Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)](https://onco.cc/pairings/lenvatinib-plus-pembrolizumab/)
- ideas: [Use imaging to find the window when tumour blood vessels are working properly](https://onco.cc/ideas/idea-bio2-vascular-normalisation-window/)

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