{"entity":{"id":"pd1-plus-chemo-pdl1-low","kind":"pairing","name":"PD-1 blockade + chemotherapy in PD-L1-low NSCLC","aka":[],"tldr":"When the tumour shows little PD-L1, immunotherapy alone is weak, but adding chemotherapy makes it work for most patients.","summary":"This combination gives a PD-1 checkpoint inhibitor together with cytotoxic chemotherapy in non-small-cell lung cancer whose PD-L1 tumour proportion score is low. Chemotherapy releases tumour antigen and depletes suppressive cells, priming an immune response that PD-1 blockade then sustains, and the benefit does not depend on the PD-L1 level. KEYNOTE-189 in non-squamous and KEYNOTE-407 in squamous disease showed an overall survival benefit across PD-L1 strata, including tumours with essentially no PD-L1 expression. POSEIDON adds tremelimumab to durvalumab and chemotherapy for PD-L1-negative and STK11- or KEAP1-mutant disease. Pembrolizumab with chemotherapy is now the standard control arm against which every new first-line lung regimen is measured.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT02142738: KEYNOTE-024 & KEYNOTE-189","url":"https://clinicaltrials.gov/study/NCT02142738"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","tremelimumab","durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":["tps"],"trials":["keynote-024-189"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"checkpoint-inhibitor","b":"cytotoxic-chemotherapy","rationale":"Chemotherapy releases antigen and depletes suppressive cells, priming a response that PD-1 blockade sustains; benefit is independent of PD-L1 level.","evidence":"Multiple phase 3 with 5-year OS data.","pairingType":"combination"},"route":"/pairings/pd1-plus-chemo-pdl1-low/","neighbours":{"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"drug":[{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}],"term":[{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"trial":[{"id":"keynote-024-189","kind":"trial","name":"KEYNOTE-024 & KEYNOTE-189","route":"/trials/keynote-024-189/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}]}}