{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:53:08Z","timestamp":1789498388264,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UG1CA189867, U10CA180868, U10CA180822, U24CA180803"],"award-info":[{"award-number":["UG1CA189867, U10CA180868, U10CA180822, U24CA180803"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","award":["UG1CA189867, U10CA180868, U10CA180822, U24CA180803"],"award-info":[{"award-number":["UG1CA189867, U10CA180868, U10CA180822, U24CA180803"]}],"id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent\/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin\u2013radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III\u2013IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted.<\/jats:p>","DOI":"10.3390\/cancers13122882","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T04:22:22Z","timestamp":1623212542000},"page":"2882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["NRG-HN003: Phase I and Expansion Cohort Study of Adjuvant Pembrolizumab, Cisplatin and Radiation Therapy in Pathologically High-Risk Head and Neck Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-6636","authenticated-orcid":false,"given":"Julie E.","family":"Bauman","sequence":"first","affiliation":[{"name":"University of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Harris","sequence":"additional","affiliation":[{"name":"NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra","family":"Uppaluri","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute and Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yao","sequence":"additional","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Ferris","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Kaiser Permanente, Dublin, CA 94568, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Jordan","sequence":"additional","affiliation":[{"name":"NRG Oncology Biospecimen Bank, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil P.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Jujjuvaparu","sequence":"additional","affiliation":[{"name":"Illinois CancerCare PC, Peoria, IL 61615, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dukagjin M.","family":"Blakaj","sequence":"additional","affiliation":[{"name":"Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Henson","sequence":"additional","affiliation":[{"name":"University of Oklahoma Health Sciences Center, University of Oklahoma, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawad","family":"Sheqwara","sequence":"additional","affiliation":[{"name":"Henry Ford Health Institute, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren K.","family":"Mell","sequence":"additional","affiliation":[{"name":"University of California San Diego Moores Cancer Center, University of California, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neilayan","family":"Sen","sequence":"additional","affiliation":[{"name":"Rush University Medical Center, Rush University, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Clump","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhur K.","family":"Garg","sequence":"additional","affiliation":[{"name":"Montefiore Medical Center, Bronx, NY 10467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emrullah","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"University of New Mexico Cancer Center, University of New Mexico, Albuquerque, NM 87102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Torres-Saavedra","sequence":"additional","affiliation":[{"name":"NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA 19102, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-1439","authenticated-orcid":false,"given":"Quynh-Thu","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Forman, D., and Bray, F. 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