{"doi":"10.1007/s00262-022-03314-1","title":"A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Background</jats:title>\n                <jats:p>CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, <jats:italic>ICAM1</jats:italic> expression, or CD3<jats:sup>+</jats:sup> infiltrates. Surprisingly, the baseline cell density of CD3<jats:sup>+</jats:sup>CD8<jats:sup>−</jats:sup> T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (<jats:italic>P</jats:italic> = 0.0179).</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>These findings suggest responses to this combination may be seen even in patients without a typical “immune-active” microenvironment.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Trial registration number</jats:title>\n                <jats:p>NCT02565992.</jats:p>\n              </jats:sec>","journal":"Cancer Immunology, Immunotherapy","year":2023,"id":647759,"datarank":1.3216888538288076,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.7348854030145856,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.7348854030145856,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":48,"citers_with_citation_signal":40,"citers_with_endowment":40,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1687816,"name":"Steven J. O’Day","orcid":null,"position":1,"is_corresponding":false},{"id":1287778,"name":"Howard L. Kaufman","orcid":"0000-0003-3538-4166","position":2,"is_corresponding":false},{"id":1687818,"name":"Jennifer Bryan","orcid":null,"position":3,"is_corresponding":false},{"id":1687820,"name":"Jacqueline T. Norrell","orcid":null,"position":4,"is_corresponding":false},{"id":688273,"name":"Casey Imbergamo","orcid":"0000-0003-0723-7089","position":5,"is_corresponding":false},{"id":653998,"name":"Daniella Portal","orcid":"0000-0001-7364-039X","position":6,"is_corresponding":false},{"id":1687825,"name":"Edwin Zambrano-Acosta","orcid":null,"position":7,"is_corresponding":false},{"id":622339,"name":"Marisa Palmeri","orcid":null,"position":8,"is_corresponding":false},{"id":1687828,"name":"Seymour Fein","orcid":null,"position":9,"is_corresponding":false},{"id":447384,"name":"Cai Wu","orcid":"0000-0001-5629-7163","position":10,"is_corresponding":false},{"id":1687832,"name":"Leslie Guerreiro","orcid":null,"position":11,"is_corresponding":false},{"id":780341,"name":"Daniel Medina","orcid":"0000-0003-4830-6941","position":12,"is_corresponding":false},{"id":425702,"name":"Praveen K. Bommareddy","orcid":"0000-0003-0089-8693","position":13,"is_corresponding":false},{"id":425705,"name":"Andrew Zloza","orcid":"0000-0001-8844-6493","position":14,"is_corresponding":false},{"id":258858,"name":"Bernard A. Fox","orcid":"0000-0002-4452-5947","position":15,"is_corresponding":false},{"id":1687842,"name":"Carmen Ballesteros-Merino","orcid":null,"position":16,"is_corresponding":false},{"id":1203821,"name":"Yixin Ren","orcid":"0000-0002-8499-4545","position":17,"is_corresponding":false},{"id":1687844,"name":"Darren Shafren","orcid":null,"position":18,"is_corresponding":false},{"id":1687846,"name":"Mark Grose","orcid":null,"position":19,"is_corresponding":false},{"id":1687848,"name":"Joshua A. Vieth","orcid":null,"position":20,"is_corresponding":false},{"id":258831,"name":"Janice M. Mehnert","orcid":"0000-0002-1043-3008","position":21,"is_corresponding":false},{"id":425697,"name":"Ann W. Silk","orcid":"0000-0003-3877-3984","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Background</jats:title>\n                <jats:p>CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, <jats:italic>ICAM1</jats:italic> expression, or CD3<jats:sup>+</jats:sup> infiltrates. Surprisingly, the baseline cell density of CD3<jats:sup>+</jats:sup>CD8<jats:sup>−</jats:sup> T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (<jats:italic>P</jats:italic> = 0.0179).</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>These findings suggest responses to this combination may be seen even in patients without a typical “immune-active” microenvironment.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Trial registration number</jats:title>\n                <jats:p>NCT02565992.</jats:p>\n              </jats:sec>","is_dataset_classified":null,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36445410","pmcid":"PMC10198910","openalex_id":"https://openalex.org/W4310206587","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01CA142779-03","title":"B7-H1/PD-1 modulation in cancer therapy"}],"total_grants":1,"fwci":6.2236,"citation_percentile":0.97194776,"influential_citations":0,"citation_trend":[{"year":2022,"count":2},{"year":2023,"count":6},{"year":2024,"count":12},{"year":2025,"count":17},{"year":2026,"count":12}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00262-022-03314-1.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s00262-022-03314-1.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00262-022-03314-1/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00262-022-03314-1","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36445410","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10198910","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10198910/pdf/262_2022_Article_3314.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10198910","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10198910?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1007/s00262-022-03314-1","host_type":""}],"fields_of_study":["Virus-based gene therapy research","Immunotherapy and Immune Responses","Cancer Immunotherapy and Biomarkers","0301 basic medicine","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Animals","Goats","Humans","Melanoma","Oncolytic Viruses","Tumor Microenvironment","Antibodies, Monoclonal, Humanized"],"keywords":["Pembrolizumab","Medicine","Oncolytic virus","Internal medicine","Tumor microenvironment","Oncology","Adverse effect","CD8","Immunotherapy","Clinical endpoint","Melanoma","Gastroenterology","Immunology","Immune system","Cancer","Clinical trial","Cancer research","V937","Oncolytic Viruses","Research","Goats","Humans","Animals","Antibodies, Monoclonal, Humanized"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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