{"id":17056,"date":"2024-10-01T10:47:40","date_gmt":"2024-10-01T08:47:40","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/10\/01\/a-phase-1-trial-of-trebananib-an-angiopoietin-1-and-2-neutralizing-peptibody-combined-with-pembrolizumab-in-patients-with-advanced-ovarian-and-colorectal-cancer\/"},"modified":"2024-10-01T10:47:40","modified_gmt":"2024-10-01T08:47:40","slug":"a-phase-1-trial-of-trebananib-an-angiopoietin-1-and-2-neutralizing-peptibody-combined-with-pembrolizumab-in-patients-with-advanced-ovarian-and-colorectal-cancer","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/10\/01\/a-phase-1-trial-of-trebananib-an-angiopoietin-1-and-2-neutralizing-peptibody-combined-with-pembrolizumab-in-patients-with-advanced-ovarian-and-colorectal-cancer\/","title":{"rendered":"A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer"},"content":{"rendered":"<div>\n<p>Cancer Immunol Res. 2024 Sep 30. doi: 10.1158\/2326-6066.CIR-23-1027. Online ahead of print.<\/p>\n<p>ABSTRACT<\/p>\n<p>Ovarian cancers and microsatellite stable (MSS) colorectal cancers (CRC) are insensitive to anti-PD1 immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggests a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase 1 dose-escalation study of pembrolizumab and the angiopoietin 1\/2 inhibitor trebananib (NCT03239145). This multicenter trial enrolled patients with metastatic ovarian cancer or MSS CRC. Trebananib was administered intravenously weekly for 12 weeks with 200 mg intravenous pembrolizumab every 3 weeks. The toxicity profile of this combination was manageable, and the protocol-defined highest dose level (trebananib 30 mg\/kg weekly plus pembrolizumab 200 mg every 3 weeks) was declared the maximum tolerated dose. The objective response rate for all patients was 7.3% (90% confidence interval: 2.5-15.9%). Three patients with MSS CRC had durable responses for \u22653 years. One responding patient&#8217;s CRC harbored a POLE mutation. The other two responding patients had left-sided CRCs with no baseline liver metastases, and genomic analysis revealed that they both had KRAS wild-type, ERBB2 amplified tumors. After development of acquired resistance, biopsy of one patient&#8217;s KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39348472\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101614637&amp;ff=20241001044739&amp;v=2.18.0.post9+e462414\">39348472<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1158\/2326-6066.CIR-23-1027\">10.1158\/2326-6066.CIR-23-1027<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Cancer Immunol Res. 2024 Sep 30. doi: 10.1158\/2326-6066.CIR-23-1027. Online ahead of print. ABSTRACT Ovarian cancers and microsatellite stable (MSS) colorectal cancers (CRC) are insensitive to anti-PD1 immunotherapy, and new immunotherapeutic approaches are needed. Preclinical data suggests a relationship between immunotherapy resistance and elevated angiopoietin 2 levels. We performed a phase 1 dose-escalation study of pembrolizumab &#8230; <a title=\"A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/10\/01\/a-phase-1-trial-of-trebananib-an-angiopoietin-1-and-2-neutralizing-peptibody-combined-with-pembrolizumab-in-patients-with-advanced-ovarian-and-colorectal-cancer\/\" aria-label=\"Read more about A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[55,42],"tags":[],"class_list":["post-17056","post","type-post","status-publish","format-standard","hentry","category-cancer-immunology-reserch","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/17056","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=17056"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/17056\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=17056"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=17056"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=17056"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}