{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:48:43Z","timestamp":1790124523636,"version":"4.0.1"},"reference-count":21,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)\u2013ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg\/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, overall survival (OS), and grade \u22653 adverse events. A log-rank test was used to compare survival between arms, with a one-sided alpha of 0.1 and power of 90%. Immune biomarkers were analyzed from baseline and on treatment tissue and blood collections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The median PFS for nivolumab versus nivolumab plus ipilimumab were 2.9 months (90% CI, 1.9 to 3.8) and 3.7 months (90% CI, 2.0 to 5.6), respectively (hazard ratio [HR], 0.86 [95% CI, 0.60 to 1.23];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .25). Response rates were similar for nivolumab (17.4%) and nivolumab plus ipilimumab (21.5%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .89). The median OS was 15.9 months for nivolumab and 20.0 months for nivolumab plus ipilimumab (HR, 0.98 [90% CI, 0.63 to 1.51]). Grade \u22653 treatment-related AEs occurred in 6 patients (12%) receiving nivolumab alone and in 12 patients (25%) receiving nivolumab plus ipilimumab. At week 9, circulating TIGIT+ CD8\n                      <jats:sup>+<\/jats:sup>\n                      cells (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) increased with nivolumab plus ipilimumab treatment relative to baseline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The addition of ipilimumab to nivolumab did not statistically improve overall response rate, PFS, or OS but may harbor increased toxicity. Paired blood samples identified TIGIT expression on peripheral T cells as a compensatory change unique to dual PD-1 plus CTLA-4 blockade.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00929","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T20:59:28Z","timestamp":1767819568000},"page":"497-507","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":7,"title":["NCI9673 (Part B): ETCTN Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Refractory, Metastatic Squamous Cell Carcinoma of the Anal Canal"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct02314169","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-2252","authenticated-orcid":true,"given":"Van K.","family":"Morris","sequence":"first","affiliation":[{"name":"University of Texas\u2014MD Anderson Cancer Center, Houston, 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