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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

Cited 10 time in Web of Science Cited 10 time in Scopus
Authors

Bendell, Johanna; LoRusso, Patricia; Overman, Michael; Noonan, Anne M.; Kim, Dong-Wan; Strickler, John H.; Kim, Sang-We; Clarke, Stephen; George, Thomas J.; Grimison, Peter S.; Barve, Minal; Amin, Manik; Desai, Jayesh; Wise-Draper, Trisha; Eck, Steven; Jiang, Yu; Khan, Anis A.; Wu, Yuling; Martin, Philip; Cooper, Zachary A.; Elgeioushi, Nairouz; Mueller, Nancy; Kumar, Rakesh; Patel, Sandip Pravin

Issue Date
2023-07
Publisher
Springer Verlag
Citation
Cancer Immunology, Immunotherapy, Vol.72 No.7, pp.2443-2458
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.
ISSN
0340-7004
URI
https://hdl.handle.net/10371/192470
DOI
https://doi.org/10.1007/s00262-023-03430-6
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