{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:56:30Z","timestamp":1790736990156,"version":"4.1.0"},"reference-count":21,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["KC170216"],"award-info":[{"award-number":["KC170216"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["CA209-669"],"award-info":[{"award-number":["CA209-669"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI P30 CA051008"],"award-info":[{"award-number":["NCI P30 CA051008"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["NCI P50CA101942"],"award-info":[{"award-number":["NCI P50CA101942"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,7,15]]},"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>To determine the efficacy and toxicity of nivolumab monotherapy in treatment-na\u00efve patients with non-clear cell renal cell carcinoma (nccRCC) and the efficacy of nivolumab\/ipilimumab salvage therapy in patients with tumors unresponsive to initial nivolumab monotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Eligible patients with treatment-na\u00efve nccRCC received nivolumab until progressive disease (PD), toxicity, or completion of 96 weeks of treatment (Part A). Patients with PD prior to, or stable disease (SD) at 48 weeks (prolonged SD) were potentially eligible to receive salvage nivolumab\/ipilimumab (Part B). Patients were required to submit tissue from a metastatic lesion obtained within 12 months prior to study entry and prior to Part B for correlative studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>35 patients with nccRCC were enrolled: 19 (54%) had papillary, 6 (17%) had chromophobe and 10 (29%) had unclassified histology. At median follow-up of 22.9 months, RECIST-defined objective response rate (ORR) was 5 of 35 (14.3% 95% CI 4.8% to 30.3%) (complete response (CR) 2 (5.7%) and partial response (PR) 3 (8.6%)). ORR by histology was: papillary\u20141\/19 (5%); chromophobe\u20141\/6 (17%); and unclassified\u20143\/10 (30%). Nine patients (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified and 1 papillary) responding. ORR was 0\/18, 3\/11 (27%) and 2\/6 (33%) for patients with tumor progammed death ligand 1 (PD-L1) expression of &lt;5%, \u22655%\u2009or not measured, respectively. Median progression-free survival was 4.0 (2.7\u20134.3) months. Two of five responders have progressed. Thirty-two patients had PD or prolonged SD and therefore, were potentially eligible for salvage nivolumab\/ipilimumab (Part B), but 15 patients did not enroll due to grade 2\u20133 toxicity (6) on nivolumab, symptomatic disease progression (5), or other reasons including no biopsy tissue (4). In the 17 Part B patients, there was one PR (6%) (unclassified\/non-sarcomatoid). Grade <jats:underline>&gt;<\/jats:underline>3 treatment-related adverse events were seen in 7\/35 (20%) on nivolumab and 7\/17 (41%) on salvage nivolumab\/ipilimumab with one patient experiencing sudden death.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nivolumab monotherapy has limited activity in treatment-na\u00efve nccRCC with most responses (4 of 5) seen in patients with sarcomatoid and\/or unclassified tumors. Toxicity is consistent with prior nivolumab studies. Salvage treatment with nivolumab\/ipilimumab was provided in half of these patients with minimal activity.<\/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=\"NCT03117309\">NCT03117309<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-004780","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T18:28:50Z","timestamp":1683656930000},"page":"e004780","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Phase II study of nivolumab and salvage nivolumab\/ipilimumab in treatment-na\u00efve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct03117309","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04413123","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03866382","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04704219","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05043090","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-9924","authenticated-orcid":false,"given":"Michael B","family":"Atkins","sequence":"first","affiliation":[{"name":"Oncology, Georgetown University, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi A","family":"Jegede","sequence":"additional","affiliation":[{"name":"Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi B","family":"Haas","sequence":"additional","affiliation":[{"name":"Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F","family":"McDermott","sequence":"additional","affiliation":[{"name":"Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4003-1103","authenticated-orcid":false,"given":"Mehmet A","family":"Bilen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stein","sequence":"additional","affiliation":[{"name":"Oncology, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A","family":"Sosman","sequence":"additional","affiliation":[{"name":"Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Alter","sequence":"additional","affiliation":[{"name":"Hematology Oncology, John Theurer Cancer Center, Hackensack, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R","family":"Plimack","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0184-3467","authenticated-orcid":false,"given":"Moshe C","family":"Ornstein","sequence":"additional","affiliation":[{"name":"Hematology Oncology, Taussig Cancer Institute, Cleveland, Ohio, 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