{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:30:09Z","timestamp":1779309009427,"version":"3.51.4"},"reference-count":36,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Alligator Bioscience AB","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,12,14]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>ATOR-1017 (evunzekibart) is a human agonistic immunoglobulin G4 antibody targeting the costimulatory receptor 4-1BB (CD137). ATOR-1017 activates T cells and natural killer cells in the tumor environment, leading to immune-mediated tumor cell death.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this first-in-human, multicenter, phase I study, ATOR-1017 was administered intravenously every 21 days as a monotherapy to patients with advanced, unresectable solid tumors having received multiple standard-of-care treatments. The study used single patient cohorts for rapid dose escalation up to 40\u2009mg; thereafter a modified 3+3 design up to 900\u2009mg. Escalating doses were given until disease progression, unacceptable toxicity, or withdrawal of consent. The primary objective of the study included determination of the maximum tolerated dose (MTD) via assessment of adverse events and dose-limiting toxicities (DLTs). Secondary objectives included determination of the pharmacokinetics, immunogenicity and clinical efficacy assessed with CT scans using immune Response Evaluation Criteria in Solid Tumors. Exploratory objectives included pharmacodynamic (PD) assessment of immune system biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of the 27 patients screened, 25 received treatment with ATOR-1017. The median time on study was 13.1 weeks (range 4.3\u201392.3). The MTD of ATOR-1017 was not reached. Treatment-related adverse events (TRAEs) were reported in 13 (52%) of 25 patients; most common (\u226510%) were fatigue (n=4 (16.0%) patients) and neutropenia (n=3 (12.0%) patients). Five patients experienced a severe (\u2265 grade 3) TRAE; neutropenia (n=2), febrile neutropenia (n=1), chest pain (n=1), increased liver enzymes (n=1), and leukopenia and thrombocytopenia (n=1). No patients discontinued due to TRAEs and no DLTs were observed. Pharmacokinetic data demonstrated approximate dose-proportional kinetics. Dose-dependent increases in PD biomarkers, including soluble 4-1BB, are indicative of target-mediated biological activity. Best response was stable disease in 13 out of 25 patients (52%), maintained for 6\u2009months or longer in six patients (24%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Treatment with ATOR-1017 was safe and well tolerated at all dose levels and demonstrated biological activity. Furthermore, almost one-third of patients experienced long-lasting stable disease in this heavily pretreated population. The encouraging safety and preliminary efficacy data warrant further clinical development of ATOR-1017, possibly in combination with other anticancer agents.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-010113","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T03:15:24Z","timestamp":1737602124000},"page":"e010113","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["First-in-human, multicenter, open-label, phase I study of ATOR-1017 (evunzekibart), a 4-1BB antibody, in patients with advanced solid malignancies"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct04144842","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ana","family":"Carneiro","sequence":"first","affiliation":[{"name":"Sk\u00e5ne University Hospital and Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Oncology, Uppsala University Hospital, Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-1250","authenticated-orcid":false,"given":"Peter","family":"Ellmark","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB, Lund, Sweden"},{"name":"Department of Immunotechnolgy, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Enell Smith","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Schultz","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumeet","family":"Ambarkhane","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Yachnin","sequence":"additional","affiliation":[{"name":"Karolinska Institute, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-3267","authenticated-orcid":false,"given":"Gustav J.","family":"Ullenhag","sequence":"additional","affiliation":[{"name":"Department of Oncology, Uppsala University Hospital, Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, 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