{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T18:40:06Z","timestamp":1794249606895,"version":"4.9.0"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072558"],"award-info":[{"award-number":["82072558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241232"],"award-info":[{"award-number":["82241232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272789"],"award-info":[{"award-number":["82272789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eClinicalMedicine"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.eclinm.2023.102106","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T12:43:08Z","timestamp":1691066588000},"page":"102106","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":121,"special_numbering":"C","title":["AK112, a novel PD-1\/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial"],"prefix":"10.1016","volume":"62","author":[{"given":"Yuanyuan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongmin Maxwell","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-0761","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.eclinm.2023.102106_bib1","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1158\/1078-0432.CCR-21-3844","article-title":"FDA approval summary: pembrolizumab, atezolizumab, and cemiplimab-rwlc as single agents for first-line treatment of advanced\/metastatic PD-L1-high NSCLC","volume":"28","author":"Akinboro","year":"2022","journal-title":"Clin Cancer Res"},{"issue":"14","key":"10.1016\/j.eclinm.2023.102106_bib2","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMoa1917346","article-title":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","volume":"383","author":"Herbst","year":"2020","journal-title":"N\u00a0Engl J Med"},{"issue":"10183","key":"10.1016\/j.eclinm.2023.102106_bib3","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.eclinm.2023.102106_bib4","doi-asserted-by":"crossref","first-page":"S1182","DOI":"10.1016\/j.annonc.2020.08.2285","article-title":"LBA52 EMPOWER-Lung 1: phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) \u226550%","volume":"31","author":"Sezer","year":"2020","journal-title":"Ann Oncol"},{"issue":"6","key":"10.1016\/j.eclinm.2023.102106_bib5","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1200\/JCO.21.01497","article-title":"First-line immunotherapy for non-small-cell lung cancer","volume":"40","author":"Reck","year":"2022","journal-title":"J\u00a0Clin Oncol"},{"issue":"24","key":"10.1016\/j.eclinm.2023.102106_bib6","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1056\/NEJMoa1716948","article-title":"Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N\u00a0Engl J Med"},{"issue":"2","key":"10.1016\/j.eclinm.2023.102106_bib7","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N\u00a0Engl J Med"},{"issue":"10","key":"10.1016\/j.eclinm.2023.102106_bib8","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1056\/NEJMoa0810699","article-title":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","volume":"361","author":"Mok","year":"2009","journal-title":"N\u00a0Engl J Med"},{"issue":"11","key":"10.1016\/j.eclinm.2023.102106_bib9","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/S1470-2045(17)30608-3","article-title":"Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial","volume":"18","author":"Wu","year":"2017","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.eclinm.2023.102106_bib10","series-title":"NCCN clinical practice guidelines in oncology (NCCN Guidelines\u00ae) Non-small cell lung cancer. Version 1.2023","year":"2022"},{"key":"10.1016\/j.eclinm.2023.102106_bib11","doi-asserted-by":"crossref","first-page":"S837","DOI":"10.1016\/j.annonc.2020.08.1607","article-title":"1293P IMpower150: updated efficacy analysis in patients with EGFR mutations","volume":"31","author":"Reck","year":"2020","journal-title":"Ann Oncol"},{"issue":"5","key":"10.1016\/j.eclinm.2023.102106_bib12","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S2213-2600(19)30084-0","article-title":"Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial","volume":"7","author":"Reck","year":"2019","journal-title":"Lancet Respir Med"},{"issue":"9","key":"10.1016\/j.eclinm.2023.102106_bib13","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S1470-2045(22)00382-5","volume":"23","author":"Lu","year":"2022","journal-title":"Lancet Oncol"},{"issue":"4","key":"10.1016\/j.eclinm.2023.102106_bib14","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/S1556-0864(23)00260-5","article-title":"60 CONTACT-01: efficacy and safety from a phase III study of atezolizumab (atezo)\u00a0+ cabozantinib (cabo) vs docetaxel (doc) monotherapy in patients (pts) with metastatic NSCLC (mNSCLC) previously treated with checkpoint inhibitors and chemotherapy","volume":"18","author":"Neal","year":"2023","journal-title":"J\u00a0Thorac Oncol"},{"issue":"21","key":"10.1016\/j.eclinm.2023.102106_bib15","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1200\/JCO.22.00912","article-title":"Phase II randomized study of ramucirumab and pembrolizumab versus standard of care in advanced non-small-cell lung cancer previously treated with immunotherapy-lung-MAP S1800A","volume":"40","author":"Reckamp","year":"2022","journal-title":"J\u00a0Clin Oncol"},{"issue":"2","key":"10.1016\/j.eclinm.2023.102106_bib16","article-title":"SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer","volume":"11","author":"Zhao","year":"2023","journal-title":"J\u00a0Immunother Cancer"},{"issue":"1","key":"10.1016\/j.eclinm.2023.102106_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4174\/astr.2015.89.1.1","article-title":"Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis","volume":"89","author":"Lee","year":"2015","journal-title":"Ann Surg Treat Res"},{"issue":"5","key":"10.1016\/j.eclinm.2023.102106_bib18","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1200\/JCO.2005.06.081","article-title":"Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis","volume":"23","author":"Hicklin","year":"2005","journal-title":"J\u00a0Clin Oncol"},{"key":"10.1016\/j.eclinm.2023.102106_bib19","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.616837","article-title":"Direct and indirect modulation of T cells by VEGF-A counteracted by anti-angiogenic treatment","volume":"12","author":"Bourhis","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.eclinm.2023.102106_bib20","doi-asserted-by":"crossref","first-page":"978","DOI":"10.3389\/fimmu.2018.00978","article-title":"Targeting VEGF\/VEGFR to modulate antitumor immunity","volume":"9","author":"Yang","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.eclinm.2023.102106_bib21","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.3389\/fimmu.2018.03081","article-title":"Vascular targeting to increase the efficiency of immune checkpoint blockade in cancer","volume":"9","author":"Georganaki","year":"2018","journal-title":"Front Immunol"},{"issue":"8","key":"10.1016\/j.eclinm.2023.102106_bib22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrc.2017.51","article-title":"Microenvironmental regulation of tumour angiogenesis","volume":"17","author":"De Palma","year":"2017","journal-title":"Nat Rev Cancer"},{"issue":"15","key":"10.1016\/j.eclinm.2023.102106_bib23","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1158\/0008-5472.CAN-17-2176","article-title":"Combined VEGF and PD-L1 blockade displays synergistic treatment effects in an autochthonous mouse model of small cell lung cancer","volume":"78","author":"Meder","year":"2018","journal-title":"Cancer Res"},{"issue":"Suppl 2","key":"10.1016\/j.eclinm.2023.102106_bib24","first-page":"A546","article-title":"AK112, a tetravalent bispecific antibody targeting PD-1 and VEGF, enhances binding avidity and functional activities and elicits potent anti-tumor efficacy in pre-clinical studies","volume":"10","author":"Zhong","year":"2022","journal-title":"J\u00a0Immunother Cancer"},{"issue":"16_suppl","key":"10.1016\/j.eclinm.2023.102106_bib25","doi-asserted-by":"crossref","first-page":"9040","DOI":"10.1200\/JCO.2022.40.16_suppl.9040","article-title":"A\u00a0phase Ib\/II study of AK112, a PD-1\/VEGF bispecific antibody, as first- or second-line therapy for advanced non\u2013small cell lung cancer (NSCLC)","volume":"40","author":"Zhou","year":"2022","journal-title":"J\u00a0Clin Oncol"},{"issue":"12","key":"10.1016\/j.eclinm.2023.102106_bib26","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1056\/NEJMoa1816714","article-title":"Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma","volume":"380","author":"Rini","year":"2019","journal-title":"N\u00a0Engl J Med"},{"issue":"6","key":"10.1016\/j.eclinm.2023.102106_bib27","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41591-018-0053-3","article-title":"Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma","volume":"24","author":"McDermott","year":"2018","journal-title":"Nat Med"},{"issue":"8","key":"10.1016\/j.eclinm.2023.102106_bib28","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1470-2045(19)30458-9","article-title":"Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a\/b trial","volume":"20","author":"Herbst","year":"2019","journal-title":"Lancet Oncol"},{"issue":"11","key":"10.1016\/j.eclinm.2023.102106_bib29","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1200\/JCO.19.01598","article-title":"Phase IB\/II trial of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma, endometrial cancer, and other selected advanced solid tumors","volume":"38","author":"Taylor","year":"2020","journal-title":"J\u00a0Clin Oncol"},{"issue":"26","key":"10.1016\/j.eclinm.2023.102106_bib30","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1200\/JCO.19.02627","article-title":"Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer","volume":"38","author":"Makker","year":"2020","journal-title":"J\u00a0Clin Oncol"},{"issue":"6","key":"10.1016\/j.eclinm.2023.102106_bib31","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1200\/JCO.22.00975","article-title":"Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study","volume":"41","author":"Johnson","year":"2023","journal-title":"J\u00a0Clin Oncol"},{"issue":"2","key":"10.1016\/j.eclinm.2023.102106_bib32","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1470-2045(20)30641-0","article-title":"First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial","volume":"22","author":"Paz-Ares","year":"2021","journal-title":"Lancet Oncol"},{"issue":"12","key":"10.1016\/j.eclinm.2023.102106_bib33","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/j.annonc.2021.08.2151","article-title":"Clinical definition of acquired resistance to immunotherapy in patients with metastatic non-small-cell lung cancer","volume":"32","author":"Schoenfeld","year":"2021","journal-title":"Ann Oncol"},{"issue":"4","key":"10.1016\/j.eclinm.2023.102106_bib34","doi-asserted-by":"crossref","first-page":"413","DOI":"10.21037\/tlcr.2019.08.09","article-title":"The association of PD-L1 expression with the efficacy of anti-PD-1\/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials","volume":"8","author":"Xu","year":"2019","journal-title":"Transl Lung Cancer Res"},{"issue":"12","key":"10.1016\/j.eclinm.2023.102106_bib35","doi-asserted-by":"crossref","first-page":"6288","DOI":"10.3390\/ijms22126288","article-title":"Anti-PD1\/PD-L1 immunotherapy for non-small cell lung cancer with actionable oncogenic driver mutations","volume":"22","author":"Dantoing","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"4","key":"10.1016\/j.eclinm.2023.102106_bib36","doi-asserted-by":"crossref","first-page":"60","DOI":"10.21037\/cco.2020.01.03","article-title":"PD-L1 expression and efficacy of pembrolizumab as monotherapy in NSCLC","volume":"9","author":"Jorgensen","year":"2020","journal-title":"Chin Clin Oncol"}],"container-title":["eClinicalMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537023002833?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589537023002833?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:20:56Z","timestamp":1762899656000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589537023002833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":36,"alternative-id":["S2589537023002833"],"URL":"https:\/\/doi.org\/10.1016\/j.eclinm.2023.102106","relation":{},"ISSN":["2589-5370"],"issn-type":[{"value":"2589-5370","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"AK112, a novel PD-1\/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial","name":"articletitle","label":"Article Title"},{"value":"eClinicalMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.eclinm.2023.102106","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"102106"}}