{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:53:14Z","timestamp":1793130794749,"version":"4.5.0"},"reference-count":25,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"unspecified","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) funded by the Korea government","award":["RS-2025-00557272"],"award-info":[{"award-number":["RS-2025-00557272"]}]},{"name":"CJ Bioscience Company","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100003569","name":"The Ministry of Food and Drug Safety","doi-asserted-by":"crossref","award":["RS-2025-02215737"],"award-info":[{"award-number":["RS-2025-02215737"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,2,16]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Background<\/jats:title>\n \n Dysbiosis of gut microbiome leads to resistance to immunotherapy in various advanced solid tumors. CJRB-101 is a live biotherapeutic product consisting of a novel strain belonging to the species\n Leuconostoc mesenteroides<\/jats:italic>\n . To modulate the tumor microenvironment, CJRB-101 was combined with pembrolizumab.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Preclinical efficacy and mechanistic studies were performed using humanized non-small cell lung cancer (NSCLC) patient-derived xenograft (PDX) models. This is a multicenter, first-in-human, two-part, phase I, open-label study of CJRB-101 (1\u00d710\n 11<\/jats:sup>\n \u2009or 4\u00d710\n 11<\/jats:sup>\n \u2009colony forming unit (CFU)\/day) plus pembrolizumab (200\u2009mg every three weeks (Q3W)) in advanced NSCLC, melanoma, and head and neck squamous cell carcinoma in both immune checkpoint inhibitor (ICI)-naive and ICI-refractory settings. The primary endpoint was to assess the dose-limiting toxicities (DLTs), adverse events, and preliminary activity of the combination treatment. Exploratory endpoints included stool metagenomics analysis and pharmacodynamics parameters.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In four PDX models, CJRB-101 with pembrolizumab demonstrated enhanced antitumor efficacy, showing a tumor growth inhibition (TGI) of 77.3% in the CJRB-101 monotherapy group and 61.9% in the combination group, which was significantly improved compared with pembrolizumab alone. A distinct M2-to-M1 repolarization was observed and validated in vitro. Notably, increased activation of cytotoxic T cells was observed, suggesting an immune-mediated antitumor mechanism of CJRB-101. A total of 42 patients were enrolled in the low-dose cohort (one capsule once a day; n=6) and high-dose cohort (two capsules two times a day, n=36). Metastatic NSCLC accounted for 86% (n=36) and 67% (n=28) of the patients were refractory to ICIs. None of the patients experienced DLT. In ICI-na\u00efve NSCLC (n=12) with programmed death-ligand 1 (PD-L1) >50%, the overall response rate (ORR) and disease control rate (DCR) were 58% and 75%, respectively. The ORR was 5% and DCR was 41% in the ICI-refractory NSCLC (n=22) with an ORR of 5% and DCR of 41%. After a median follow-up of 15.6 months and 8.9 months for ICI-na\u00efve and ICI-refractory NSCLC, the median progression-free survival was 9 months (95%\u2009CI 5.6 to not reached) and 1.8 months (95%\u2009CI 1.6 to 4.3), respectively. CJRB-101 plus pembrolizumab was well-tolerated, and none of the patients experienced grade\n ><\/jats:underline>\n 3 treatment-related adverse events.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Early clinical data show encouraging antitumor response of CJRB-101 plus pembrolizumab in ICI-na\u00efve metastatic NSCLC with PD-L1\n ><\/jats:underline>\n 50%.\n <\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT05877430<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jitc-2025-014702","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:25:18Z","timestamp":1778894718000},"page":"e014702","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Phase I trial of CJRB-101 plus pembrolizumab in patients with metastatic non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05877430","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05877430","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jii Bum","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujeong","family":"Baek","sequence":"additional","affiliation":[{"name":"Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-2369","authenticated-orcid":false,"given":"Dong Kwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Eun","family":"Kwon","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Jongno-gu, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misako","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, University of California Irvine School of Medicine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-8055","authenticated-orcid":false,"given":"Diwakar","family":"Davar","sequence":"additional","affiliation":[{"name":"Department of Medicine and UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5855-2403","authenticated-orcid":false,"given":"Hyunkyung","family":"Park","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjeong","family":"Kim","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Im","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9814-6918","authenticated-orcid":false,"given":"Junwon","family":"Yang","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunchong","family":"Yang","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga-Hyun","family":"Shin","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soeun","family":"Choi","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Kwon","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Min","family":"Kim","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Yeong","family":"Kang","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngtaek","family":"Kim","sequence":"additional","affiliation":[{"name":"Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Park","sequence":"additional","affiliation":[{"name":"Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"},{"name":"Yonsei New Il Han Institute for Integrative Lung Cancer Research, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Seok","family":"Oh","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Chalita","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arim","family":"Min","sequence":"additional","affiliation":[{"name":"CJ Bioscience, Inc, Seoul, Korea (the Republic 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