{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T03:52:18Z","timestamp":1788666738147,"version":"build-2803163510"},"reference-count":30,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Anaveon AG","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":[[2023,10,6]]},"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>ANV419 is a stable antibody\u2013cytokine fusion protein consisting of interleukin-2 (IL-2) fused to an anti-IL-2 monoclonal antibody that sterically hinders binding of IL-2 to the \u03b1 subunit of its receptor but has selective affinity for the receptor \u03b2\u03b3 subunits. Thus, ANV419 preferentially stimulates CD8<jats:sup>+<\/jats:sup> effector T cells and natural killer cells which are associated with tumor killing, while minimizing the activation of immunosuppressive regulatory T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>ANV419-001 is an open-label, multicenter, phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ANV419. Secondary objectives were to characterize the pharmacokinetics, pharmacodynamics and tumor response. Adult patients with advanced solid tumors and disease progression after \u22651 previous line of systemic therapy were enrolled. ANV419 was administered by intravenous infusion once every 2 weeks, with a planned treatment duration of 12 months. The dose escalation part of the study explored doses 3, 6 and 12\u2009\u00b5g\/kg as single patient cohorts followed by 24\u2013364\u2009\u00b5g\/kg in a 3+3 design. Interim results are reported here (data cut-off: March 22, 2023).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Forty patients were enrolled and received at least one dose of ANV419. The MTD and RP2D were determined to be 243\u2009\u00b5g\/kg. The most common ANV419-related treatment-emergent adverse events were Grade 1 and 2 fever (31 (77.5%)), chills (23 (57.5%), vomiting (14 (35.0%)), cytokine release syndrome and nausea (12 (30.0%) each). Transient and self-limiting lymphopenia due to lymphocyte redistribution was observed in all patients. In the RP2D cohort, Grade \u22653 thrombocytopenia and fever were reported by one patient (12.5%) each. All events were manageable with standard supportive care. At doses of 243\u2009\u00b5g\/kg (RP2D\/MTD), the estimated T<jats:sub>1\/2<\/jats:sub> was approximately 12 hours. At ANV419 doses \u2265108\u2009\u00b5g\/kg, 64% of patients had a best response of at least SD (15 SD and 1 confirmed PR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ANV419 at doses up to 243\u2009\u00b5g\/kg (the RP2D) was well tolerated and showed signs of antitumor activity in a heavily pretreated patient population with advanced solid tumors.<\/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=\"NCT04855929\">NCT04855929<\/jats:ext-link>.<\/jats:p>\n               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