{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:31:20Z","timestamp":1791955880023,"version":"4.3.4"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"unspecified","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009945","name":"Merck KGaA","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,4,7]]},"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with a high risk of metastasis. In 2017, avelumab (anti\u2013programmed death-ligand 1 (PD-L1)) became the first approved treatment for patients with metastatic MCC (mMCC), based on the occurrence of durable responses in a subset of patients. Here, we report long-term efficacy and safety data and exploratory biomarker analyses in patients with mMCC treated with avelumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In a cohort of this single-arm, phase 2 trial (JAVELIN Merkel 200), patients with mMCC and disease progression after prior chemotherapy received avelumab 10\u2009mg\/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent review per Response Evaluation Criteria in Solid Tumors V.1.1. Other assessments included duration of response, progression-free survival, overall survival (OS), safety and biomarker analyses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>As of 14 September 2018, 88 patients had been followed up for a median of 40.8 months (range 36.4\u201349.7 months). The ORR was 33.0% (95% CI 23.3% to 43.8%), including a complete response in 11.4% (10 patients), and the median duration of response was 40.5 months (95%\u2009CI 18.0 months to not estimable). As of 2 May 2019 (\u226544 months of follow-up), the median OS was 12.6 months (95%\u2009CI 7.5 to 17.1 months) and the 42-month OS rate was 31% (95% CI 22% to 41%). Of long-term survivors (OS &gt;36 months) evaluable for PD-L1 expression status (n=22), 81.8% had PD-L1+ tumors. In exploratory biomarker analyses, high tumor mutational burden (\u22652 non-synonymous somatic variants per megabase) and high major histocompatibility complex class I expression (30% of tumors with highest expression) were associated with trends for improved ORR and OS. In long-term safety assessments (\u226536 months of follow-up), no new or unexpected adverse events were reported, and no treatment-related deaths occurred.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Avelumab showed continued durable responses and meaningful long-term survival outcomes in patients with mMCC, reinforcing avelumab as a standard-of-care treatment option for this disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02155647\">NCT02155647<\/jats:ext-link>\n                  <\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-000674","type":"journal-article","created":{"date-parts":[[2020,5,15]],"date-time":"2020-05-15T16:23:15Z","timestamp":1589559795000},"page":"e000674","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":169,"title":["Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial"],"prefix":"10.1136","volume":"8","clinical-trial-number":[{"clinical-trial-number":"nct02155647","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02155647","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03271372","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-3783","authenticated-orcid":false,"given":"Sandra P","family":"D'Angelo","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan 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M","family":"Mehnert","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Terheyden","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent C","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sarah Cannon Research Institute, Nashville, Tennessee, USA"},{"name":"Department of Medical Oncology, Tennessee Oncology, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0090-9914","authenticated-orcid":false,"given":"Isaac","family":"Brownell","sequence":"additional","affiliation":[{"name":"Dermatology Branch, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Lebb\u00e9","sequence":"additional","affiliation":[{"name":"Dermatologie, Universit\u00e9 de Paris, INSERM U976, Paris, France"},{"name":"Dermatology and CIC, AP-HP, Saint Louis Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl D","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald P","family":"Linette","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Milella","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS Regina Elena National Cancer Institute, Rome, 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