{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:08:37Z","timestamp":1784740117331,"version":"3.55.0"},"reference-count":42,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T00:00:00Z","timestamp":1692403200000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,6,16]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+\u2009beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided \u03b1 of 0.05, and a power of 85%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90%\u2009CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95%\u2009CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation\/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation\/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3\u20134 TEAEs occurred in 40.6% (28\/69) of patients. Grades 3\u20134 immune-related AEs occurred in 5 (7.2%) patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for <jats:italic>EGFR<\/jats:italic>-mutated non-squamous NSCLC after EGFR TKI failure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-006887","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T07:50:10Z","timestamp":1692431410000},"page":"e006887","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Tislelizumab plus chemotherapy for patients with <i>EGFR<\/i>-mutated non-squamous non-small cell lung cancer who progressed on EGFR tyrosine kinase inhibitor therapy"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04405674","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Hua","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panwen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China"},{"name":"Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqing","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China"},{"name":"Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University\/Henan Cancer Hospital, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University\/Henan Cancer Hospital, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Phase I Clinical Trials Center, Shandong Cancer Hospital Afiliated to Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology, Shandong Cancer Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University\/Henan Cancer Hospital, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3950-3030","authenticated-orcid":false,"given":"Baohui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,8,18]]},"reference":[{"key":"2025100305491045000_11.8.e006887.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"2025100305491045000_11.8.e006887.2","first-page":"2892","article-title":"EGFR Mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by Ethnicity (mutMapII)","volume":"5","author":"Midha","year":"2015","journal-title":"Am J Cancer Res"},{"key":"2025100305491045000_11.8.e006887.3","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt205"},{"key":"2025100305491045000_11.8.e006887.4","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000033"},{"key":"2025100305491045000_11.8.e006887.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2007.00607.x"},{"key":"2025100305491045000_11.8.e006887.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909530"},{"key":"2025100305491045000_11.8.e006887.7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.36.8456"},{"key":"2025100305491045000_11.8.e006887.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612674"},{"key":"2025100305491045000_11.8.e006887.9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"2025100305491045000_11.8.e006887.10","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0025"},{"key":"2025100305491045000_11.8.e006887.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00121-7"},{"key":"2025100305491045000_11.8.e006887.12","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-020-00881-7","article-title":"Emerging therapeutic agents for advanced non-small cell lung cancer","volume":"13","author":"Chen","year":"2020","journal-title":"J Hematol Oncol"},{"key":"2025100305491045000_11.8.e006887.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.10.007"},{"key":"2025100305491045000_11.8.e006887.14","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","volume":"7","author":"Reck","year":"2019","journal-title":"The Lancet Respiratory Medicine"},{"key":"2025100305491045000_11.8.e006887.15","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S1470-2045(22)00382-5","article-title":"Sintilimab plus Bevacizumab Biosimilar Ibi305 and chemotherapy for patients with EGFR-Mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, Multicentre, phase 3 trial","volume":"23","author":"Lu","year":"2022","journal-title":"Lancet Oncol"},{"key":"2025100305491045000_11.8.e006887.16","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/2211-5463.13102","article-title":"Tislelizumab uniquely binds to the CC' loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage","volume":"11","author":"Hong","year":"2021","journal-title":"FEBS Open Bio"},{"key":"2025100305491045000_11.8.e006887.17","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00262-018-2160-x","article-title":"The binding of an anti-PD-1 antibody to Fcgammariota has a profound impact on its biological functions","volume":"67","author":"Zhang","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"2025100305491045000_11.8.e006887.18","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/jamaoncol.2021.0366","article-title":"Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: A phase 3 randomized clinical trial","volume":"7","author":"Wang","year":"2021","journal-title":"JAMA Oncol"},{"key":"2025100305491045000_11.8.e006887.19","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.jtho.2021.05.005","article-title":"Tislelizumab plus chemotherapy as first-line treatment for locally advanced or metastatic Nonsquamous NSCLC","volume":"16","author":"Lu","year":"2021","journal-title":"Journal of Thoracic Oncology"},{"key":"2025100305491045000_11.8.e006887.20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0585"},{"key":"2025100305491045000_11.8.e006887.21","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2025100305491045000_11.8.e006887.22","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"2025100305491045000_11.8.e006887.23","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"2025100305491045000_11.8.e006887.24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004873","article-title":"Cnvkit: genome-wide copy number detection and visualization from targeted DNA sequencing","volume":"12","author":"Talevich","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"2025100305491045000_11.8.e006887.25","unstructured":"Greenwood M . The natural duration of cancer. Reports of Public Health and Related Subjects. London: HMSO, 1926."},{"key":"2025100305491045000_11.8.e006887.26","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-021-00751-9","article-title":"Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial","volume":"6","author":"Jiang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2025100305491045000_11.8.e006887.27","doi-asserted-by":"crossref","DOI":"10.1016\/j.annonc.2022.08.060","article-title":"Lba58 - Sintilimab with or without Ibi305 plus chemotherapy in patients with EGFR Mutated non-squamous non-small cell lung cancer (Egfrm nsqNSCLC) who progressed on EGFR tyrosine-kinase inhibitors (Tkis) therapy: second interim analysis of phase III ORIENT-31 study","volume":"33","author":"Lu","year":"2022","journal-title":"Annals of Oncology"},{"key":"2025100305491045000_11.8.e006887.28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.5848"},{"key":"2025100305491045000_11.8.e006887.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810865"},{"key":"2025100305491045000_11.8.e006887.30","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30167-6"},{"key":"2025100305491045000_11.8.e006887.31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1200\/JCO.22.00727","article-title":"Toripalimab plus chemotherapy for patients with treatment-naive advanced non-small-cell lung cancer: A multicenter randomized phase III trial (CHOICE-01)","volume":"41","author":"Wang","year":"2023","journal-title":"J Clin Oncol"},{"key":"2025100305491045000_11.8.e006887.32","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32531-9"},{"key":"2025100305491045000_11.8.e006887.33","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1097\/JTO.0b013e3181d5e39e","article-title":"A dose finding study of weekly and Every-3-week NAB-paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer","volume":"5","author":"Socinski","year":"2010","journal-title":"Journal of Thoracic Oncology"},{"key":"2025100305491045000_11.8.e006887.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61497-5"},{"key":"2025100305491045000_11.8.e006887.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.09.014"},{"key":"2025100305491045000_11.8.e006887.36","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1038\/s41591-022-02047-z","article-title":"Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer","volume":"28","author":"Jee","year":"2022","journal-title":"Nat Med"},{"key":"2025100305491045000_11.8.e006887.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24068-x"},{"key":"2025100305491045000_11.8.e006887.38","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.836891","article-title":"Applications of circulating tumor DNA in immune Checkpoint inhibition: emerging roles and future perspectives","volume":"12","author":"Lu","year":"2022","journal-title":"Front Oncol"},{"key":"2025100305491045000_11.8.e006887.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0573-8"},{"key":"2025100305491045000_11.8.e006887.40","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003402","article-title":"Pi3K activation allows immune evasion by promoting an inhibitory myeloid tumor Microenvironment","volume":"10","author":"Collins","year":"2022","journal-title":"J Immunother Cancer"},{"key":"2025100305491045000_11.8.e006887.41","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-002279","article-title":"Cancer Immunotherapy with Pi3K and PD-1 dual-blockade via optimal modulation of T cell activation signal","volume":"9","author":"Isoyama","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2025100305491045000_11.8.e006887.42","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2293"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2023-006887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:49:21Z","timestamp":1759495761000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2023-006887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,18]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/jitc-2023-006887"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2023-006887","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}