{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:41:23Z","timestamp":1782283283684,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We conducted a phase I\/II study to evaluate durvalumab (D; anti-PD-L1) in combination with tremelimumab (T; anti\u2013cytotoxic T-lymphocyte antigen 4) in pediatric patients with relapsed\/refractory solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>The dose-finding phase (phase I) assessed the safety and pharmacokinetics of D+T at two dose levels to determine the recommended phase II dose (RP2D). The primary endpoint for the dose-expansion phase (phase II) was antitumor activity (by Response Evaluation Criteria in Solid Tumors v1.1) at the RP2D. Assessment of circulating cells reflecting immune cell activation was a secondary endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Based on safety and pharmacokinetic data in the dose-finding phase (n = 29), the adult-equivalent RP2D was determined as D (30 mg\/kg) + T (1 mg\/kg). In the dose-expansion phase, 21 patients (sarcoma, n = 11; solid tumors, n = 10) were treated at the RP2D. Of patients with sarcoma, none achieved an objective response and one had stable disease \u22657 weeks. Of the patients with solid tumors, one (chordoma) had a confirmed partial response (10.8 months duration) and one (renal cell carcinoma) had stable disease \u22657 weeks. Treatment-related adverse events occurred in 76% of patients (19% as grade 3 or 4). No adverse events leading to death were reported. Across both phases treatment with D+T resulted in an increase in CD4+Ki67+ T cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>D (30 mg\/kg) + T (1 mg\/kg) had limited antitumor activity in this pediatric population; however, the safety profile was manageable and consistent with the known safety profile in adult patients, with no new safety concerns identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, identifier NCT03837899; EudraCT, identifier 2018-003118-42.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1680081","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:26:45Z","timestamp":1778819205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Phase I\/II, open-label, multicenter study of durvalumab in combination with tremelimumab in pediatric patients with advanced solid tumors"],"prefix":"10.3389","volume":"16","author":[{"given":"Darren","family":"Hargrave","sequence":"first","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynley V.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Pediatric and Adolescent Oncology Drug Development Unit, Oak Centre for Children and Young People, The Royal Marsden Hospital and Division of 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