{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:36:23Z","timestamp":1792892183827,"version":"4.5.0"},"reference-count":40,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Immunocore Ltd.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,5,12]]},"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100\u00d7CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and\/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority of whom progressed on prior checkpoint inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this open-label, multicenter, phase 1b, dose-escalation trial, HLA-A*02:01-positive patients with mCM received weekly intravenous tebentafusp with increasing monthly doses of durvalumab and\/or tremelimumab starting day 15 of each cycle. The primary objective was to identify the maximum tolerated dose (MTD) or recommended phase 2 dose for each combination. Efficacy analyses were performed in all tebentafusp with durvalumab\u00b1tremelimumab treated patients with a sensitivity analysis in those who progressed on prior anti-PD(L)1 therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>85 patients were assigned to receive tebentafusp in combination with durvalumab (n=43), tremelimumab (n=13), or durvalumab and tremelimumab (n=29). Patients were heavily pretreated with a median of 3 prior lines of therapy, including 76 (89%) who received prior anti-PD(L)1. Maximum target doses of tebentafusp (68 mcg) alone or in combination with durvalumab (20\u2009mg\/kg) and tremelimumab (1\u2009mg\/kg) were tolerated; MTD was not formally identified for any arm. Adverse event profile was consistent with each individual therapy and there were no new safety signals nor treatment-related deaths. In the efficacy subset (n=72), the response rate was 14%, tumor shrinkage rate was 41% and 1-year OS rate was 76% (95% CI: 70% to 81%). The 1-year OS for triplet combination (79%; 95%\u2009CI: 71% to 86%) was similar to tebentafusp plus durvalumab (74%; 95%\u2009CI: 67% to 80%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>At maximum target doses, the safety of tebentafusp with checkpoint inhibitors was consistent with safety of each individual therapy. Tebentafusp with durvalumab demonstrated promising efficacy in heavily pretreated patients with mCM, including those who progressed on prior anti-PD(L)1.<\/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=\"NCT02535078\">NCT02535078<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-006747","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T12:37:41Z","timestamp":1686141461000},"page":"e006747","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Tebentafusp in combination with durvalumab and\/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02535078","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03070392","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01211262","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Omid","family":"Hamid","sequence":"first","affiliation":[{"name":"The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7575-6230","authenticated-orcid":false,"given":"Jessica C","family":"Hassel","sequence":"additional","affiliation":[{"name":"University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-4412","authenticated-orcid":false,"given":"Alexander N","family":"Shoushtari","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York, USA"},{"name":"Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-9706","authenticated-orcid":false,"given":"Friedegund","family":"Meier","sequence":"additional","affiliation":[{"name":"Skin Cancer Center at the National Center for Tumor Diseases and University Cancer Centre, Dresden, Germany"},{"name":"Department of Dermatology, University Hospital Carl Gustav Carus, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M","family":"Bauer","sequence":"additional","affiliation":[{"name":"Tennessee Oncology, Nashville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April K S","family":"Salama","sequence":"additional","affiliation":[{"name":"Duke University, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center Cancer Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo A","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C","family":"Lorigan","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Mauch","sequence":"additional","affiliation":[{"name":"University Hospital Cologne, Cologne, 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