{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:59:22Z","timestamp":1791665962984,"version":"4.3.4"},"reference-count":23,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"SWOG Operations Office"},{"name":"National Institutes of Health, National Cancer Institute","award":["CA180819"],"award-info":[{"award-number":["CA180819"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["CA180821"],"award-info":[{"award-number":["CA180821"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["CA180828"],"award-info":[{"award-number":["CA180828"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["CA180888"],"award-info":[{"award-number":["CA180888"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["CA233320"],"award-info":[{"award-number":["CA233320"]}]},{"name":"National Institutes of Health, National Cancer Institute","award":["CA233331"],"award-info":[{"award-number":["CA233331"]}]},{"name":"Bristol-Myers Squibb Company","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"ICAN-International Cancer Advocacy Network","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ms. Marcia Horn, JD","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":[[2024,7,9]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI\/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design\/setting<\/jats:title>\n                  <jats:p>A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across &gt;1,000 National Clinical Trial Network sites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>21 eligible patients were registered. Median age was 53 years (range 26\u201369); 16 (76%) were women.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>Ipilimumab 1\u2009mg\/kg intravenously every 6 weeks with nivolumab 240\u2009mg intravenously every 2 weeks was administered until disease progression, symptomatic deterioration, treatment delay for any reason &gt;56\u2009days, unacceptable or immune-related toxicity with inability to decrease prednisone to &lt;10\u2009mg daily, or per patient request.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>The primary endpoint was the overall response rate (ORR) (RECIST V.1.1). Secondary endpoints include clinical benefit rate (CBR) (includes stable disease (SD)&gt;6 months), progression-free survival (PFS), overall survival (OS), and toxicity. Immune-related outcomes included immune ORR (iORR), immune CBR (iCBR), and immune PFS (iPFS). A two-stage design was used assuming: null=5% alternative=30%, n=6 in the first stage, 16 max, one-sided alpha=13%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The median number of prior therapy lines was 2 (range: 1\u20139). 3 of 21 patients attained confirmed partial response (PR) (ORR=14%). In addition, one patient had an unconfirmed PR; one, stable disease (SD)&gt;6 months; one, immune-related RECIST (iRECIST) PR (iPR); and one patient attained iSD&gt;6 months: clinical benefit rate (response or SD&gt;6 months)=5\/21 (24%), iORR=4\/21 (19%), iCBR=7\/21 (33%). The 6-month PFS was 24%; 6-month iPFS, 33%. The PFS for patients (N=7) with iRECIST clinical benefit were 57, 52, 18, 15, 13, 7, and 7 months. The 6-month OS was 76%; the median OS, was 15.8 months. The most common toxicities were fatigue (62%) and rash (38%), and the most common grade 3\/4 immune-related adverse events were hepatic dysfunction (9.5%) and adrenal insufficiency (9.5%). Treatment-related adverse events leading to discontinuation of therapy in four patients (21%). There were no grade 5 adverse events.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Ipilimumab plus nivolumab is active in refractory metastatic adrenocortical cancer meeting the primary endpoint of the study, with a 19% iORR and 33% iCBR (includes SD\/iSD&gt;6 months) and with the longest PFS\/iPFS of 52 and 57 months.<\/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=\"NCT02834013\">NCT02834013<\/jats:ext-link> (registered 15 July, 2016; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02834013\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02834013<\/jats:ext-link>).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-009074","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T06:55:19Z","timestamp":1722063319000},"page":"e009074","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Phase II basket trial of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609: adrenocortical carcinoma cohort"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02834013","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-4840","authenticated-orcid":false,"given":"Sandip P","family":"Patel","sequence":"first","affiliation":[{"name":"Moores Cancer Center, University of California San Diego, La Jolla, California, 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