{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:59:29Z","timestamp":1792292369861,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["70113416"],"award-info":[{"award-number":["70113416"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with BRAF wildtype metastatic melanoma who exhibit primary resistance to immune checkpoint inhibitors (ICIs) have a poor prognosis. Chemotherapy has been shown to induce genetic mutations, modify the tumour microenvironment and microbiome, and influence immune system activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate in a prospective multicentre phase II trial whether two applications of an alkylating agent (dacarbazine) can sensitize patients with metastatic melanoma who are nonresponsive to ICIs to the same checkpoint inhibitor regime.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PROMIT trial (NCT04225390) enrolled patients with histologically confirmed BRAF wildtype metastatic melanoma who exhibited primary resistance to ICI therapy. Following radiological evidence of primary resistance to ICI (ipilimumab + nivolumab or pembrolizumab) upon the first staging after initiation, patients received two doses of dacarbazine at 850\u2005mg m\u20132 intravenously on days 1 and 21. Subsequently, 1 week after application of the second dose of dacarbazine, patients were rechallenged with the same ICI therapy to which they had previously shown progressive disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 53 patients were enrolled across four German skin cancer centres. Of these patients, 38 were evaluable for efficacy, having received at least one dose of ICI re-exposure. The overall objective response rate was 18% (95% confidence interval 0.08\u20130.34), with 7 of 38 patients achieving a partial response. The disease control rate was 37%. Therapy was well tolerated, with treatment-related \u2265 grade 3 CTCAE adverse events occurring in 10% of patients. No new safety signals were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study indicates that short-term chemotherapy followed by ICI rechallenge can overcome primary ICI resistance in patients with melanoma, supporting its potential as a new therapeutic option in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf350","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T11:44:42Z","timestamp":1756899882000},"page":"216-224","source":"Crossref","is-referenced-by-count":3,"title":["Breaking primary checkpoint inhibitor resistance with intermittent alkylating chemotherapy in patients with metastatic melanoma: results of a multicentre phase II 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,","place":["Germany"]},{"name":"Department of Dermatology, Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), Uniklinikum Erlangen , Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6601-6299","authenticated-orcid":false,"given":"Konstantin","family":"Drexler","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Regensburg , Regensburg ,","place":["Germany"]},{"name":"Bavarian Cancer Research Center (BZKF) , Erlangen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7129-3699","authenticated-orcid":false,"given":"Anja","family":"Gesierich","sequence":"additional","affiliation":[{"name":"Bavarian Cancer Research Center (BZKF) , Erlangen ,","place":["Germany"]},{"name":"Department of Dermatology, University Hospital W\u00fcrzburg , W\u00fcrzburg 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