{"entity":{"id":"io-plus-vegf","kind":"pairing","name":"PD-1 blockade + VEGF inhibition","aka":[],"tldr":"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.","asOf":"2026-09-04","links":[{"label":"CLEAR: lenvatinib plus pembrolizumab versus sunitinib as first treatment for advanced kidney cancer (New England Journal of Medicine 2021)","url":"https://doi.org/10.1056/NEJMoa2035716"},{"label":"ClinicalTrials.gov NCT05499390: HARMONi-2","url":"https://clinicaltrials.gov/study/NCT05499390"}],"tags":[],"related":[],"cancers":["rcc","hcc","endometrial","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["ivonescimab","atezolizumab","pembrolizumab"],"companies":[],"institutions":[],"pathways":["vegf-angiogenesis","pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"checkpoint-inhibitor","b":"antiangiogenic","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.","pairingType":"combination"},"route":"/pairings/io-plus-vegf/","neighbours":{"cancer":[{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"ivonescimab","kind":"drug","name":"Ivonescimab","route":"/drugs/ivonescimab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"vegf-angiogenesis","kind":"pathway","name":"VEGF angiogenesis","route":"/pathways/vegf-angiogenesis/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"pairing":[{"id":"lenvatinib-plus-pembrolizumab","kind":"pairing","name":"Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)","route":"/pairings/lenvatinib-plus-pembrolizumab/"}],"idea":[{"id":"idea-bio2-vascular-normalisation-window","kind":"idea","name":"Use imaging to find the window when tumour blood vessels are working properly","route":"/ideas/idea-bio2-vascular-normalisation-window/"}]}}