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First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors
DC Field | Value | Language |
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dc.contributor.author | Bendell, Johanna | - |
dc.contributor.author | LoRusso, Patricia | - |
dc.contributor.author | Overman, Michael | - |
dc.contributor.author | Noonan, Anne M. | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Strickler, John H. | - |
dc.contributor.author | Kim, Sang-We | - |
dc.contributor.author | Clarke, Stephen | - |
dc.contributor.author | George, Thomas J. | - |
dc.contributor.author | Grimison, Peter S. | - |
dc.contributor.author | Barve, Minal | - |
dc.contributor.author | Amin, Manik | - |
dc.contributor.author | Desai, Jayesh | - |
dc.contributor.author | Wise-Draper, Trisha | - |
dc.contributor.author | Eck, Steven | - |
dc.contributor.author | Jiang, Yu | - |
dc.contributor.author | Khan, Anis A. | - |
dc.contributor.author | Wu, Yuling | - |
dc.contributor.author | Martin, Philip | - |
dc.contributor.author | Cooper, Zachary A. | - |
dc.contributor.author | Elgeioushi, Nairouz | - |
dc.contributor.author | Mueller, Nancy | - |
dc.contributor.author | Kumar, Rakesh | - |
dc.contributor.author | Patel, Sandip Pravin | - |
dc.date.accessioned | 2023-05-26T01:17:10Z | - |
dc.date.available | 2023-05-26T01:17:10Z | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.created | 2023-05-19 | - |
dc.date.issued | 2023-07 | - |
dc.identifier.citation | Cancer Immunology, Immunotherapy, Vol.72 No.7, pp.2443-2458 | - |
dc.identifier.issn | 0340-7004 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192470 | - |
dc.description.abstract | BackgroundCD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1 lambda monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).MethodsPatients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.Results192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively; the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively; 6-month progression-free survival rates were 5.4, 13.2, and 16.0%.ConclusionsOleclumab +/- durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. | - |
dc.language | 영어 | - |
dc.publisher | Springer Verlag | - |
dc.title | First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s00262-023-03430-6 | - |
dc.citation.journaltitle | Cancer Immunology, Immunotherapy | - |
dc.identifier.wosid | 000963123100001 | - |
dc.identifier.scopusid | 2-s2.0-85151568745 | - |
dc.citation.endpage | 2458 | - |
dc.citation.number | 7 | - |
dc.citation.startpage | 2443 | - |
dc.citation.volume | 72 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordAuthor | Adenosine | - |
dc.subject.keywordAuthor | CD73 | - |
dc.subject.keywordAuthor | Monoclonal antibody | - |
dc.subject.keywordAuthor | Oleclumab | - |
dc.subject.keywordAuthor | Tumor microenvironment | - |
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