{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:57:56Z","timestamp":1793858276508,"version":"4.6.1"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:00:00Z","timestamp":1708732800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007313","name":"University of Texas MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["UM1Award#UM1CA186688"],"award-info":[{"award-number":["UM1Award#UM1CA186688"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sapanisertib is a potent ATP\u2010competitive, dual inhibitor of mTORC1\/2. Ziv\u2010aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF\u20101\u03b1 inhibition in combination with anti\u2010angiogenic therapy is a promising anti\u2010tumor strategy. This Phase 1 dose\u2010escalation\/expansion study assessed safety\/ tolerability of sapanisertib in combination with ziv\u2010aflibercept in advanced solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010five patients with heavily pre\u2010treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age was 62 (range: 21\u201379), and ECOG PS was 0 (9, 16%) or 1 (46, 84%). Most common tumor types included ovarian (8), colorectal (8), sarcoma (8), breast (3), cervical (4), and endometrial (4). Median number of prior lines of therapy was 4 (range 2\u201311). Sapanisertib 4\u2009mg orally 3\u2009days on and 4\u2009days off plus 3\u2009mg\/kg ziv\u2010aflibercept IV every 2\u2009weeks on a 28\u2010day\u2009cycle was defined as the maximum tolerated dose. Most frequent treatment\u2010related grade\u2009\u22652 adverse events included hypertension, fatigue, anorexia, hypertriglyceridemia, diarrhea, nausea, mucositis, and serum lipase increase. There were no grade 5 events. In patients with evaluable disease (<jats:italic>n<\/jats:italic>\u2009=\u200950), 37 patients (74%) achieved stable disease (SD) as best response, two patients (4%) achieved a confirmed partial response (PR); disease control rate (DCR) (CR\u2009+\u2009SD\u2009+\u2009PR) was 78%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The combination of sapanisertib and ziv\u2010aflibercept was generally tolerable and demonstrated anti\u2010tumor activity in heavily pre\u2010treated patients with advanced malignancies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6877","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T09:09:25Z","timestamp":1708765765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Phase I study of sapanisertib (CB\u2010228\/TAK\u2010228\/MLN0128) in combination with ziv\u2010aflibercept in patients with advanced solid 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