{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:57:32Z","timestamp":1784307452546,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T00:00:00Z","timestamp":1697846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009945","name":"Merck KGaA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009945","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint blockade has shown mixed results in advanced\/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4\u20101BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4\u20101BB agonist), PF\u201004518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The primary end point in this six\u2010arm, phase 1\/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune\u2010related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the duration of response, progression\u2010free survival, and overall survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty patients were included (35% with cervical cancer, 30% with endometrial cancer, and 35% with ovarian cancer). Most patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a033; 83%) were enrolled in arms A\u2013C (no radiation). Among 35 patients who were evaluable for efficacy, the ORR was 2.9%, and the DCR was 37.1%, with a median duration of stable disease of 5.4\u00a0months (interquartile range, 4.1\u20137.3 months). Patients with cervical cancer in arm A (avelumab and utomilumab; <jats:italic>n<\/jats:italic>\u00a0=\u00a09 evaluable patients) achieved an ORR of 11% and a DCR of 78%. The median progression\u2010free survival was 2.1\u00a0months (95% CI, 1.8\u20133.5\u00a0months), and overall survival was 9.4\u00a0months (95% CI, 5.6\u201311.9\u00a0months). No dose\u2010limiting toxicities or grade 3\u20135 immune\u2010related adverse events were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings from this trial highlight that, in heavily pretreated patients with gynecologic cancer, even multidrug regimens targeting multiple immunologic pathways, although safe, did not produce significant responses. A DCR of 78% in patients with cervical cancer who received avelumab and utomilumab indicates that further research on this combination in select patients may be warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35063","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T07:24:21Z","timestamp":1697873061000},"page":"400-409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Phase 1\/2 trial of avelumab combined with utomilumab (4\u20101BB agonist), PF\u201004518600 (OX40 agonist), or radiotherapy in patients with advanced gynecologic malignancies"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-2293","authenticated-orcid":false,"given":"Anne","family":"Knisely","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center  Houston Texas 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University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Alshawa","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecaterina E.","family":"Dumbrava","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhee","family":"Song","sequence":"additional","affiliation":[{"name":"Department of 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