NSGO-OV-UMB1/ENGOT-OV30: A phase II study of durvalumab in combination with the anti-CD73 monoclonal antibody Oleclumab in patients with relapsed ovarian cancer.

Autor: Mirza MR; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Nordic Society of Gynaecological Oncology Clinical Trial Unit (NSGO-CTU), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: mansoor.raza.mirza@regionh.dk., Tandaric L; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Henriksen JR; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Vejle, Denmark., Mäenpää J; Department of Obstetrics and Gynecology and Tays Cancer Centre, Tampere University Hospital and Tampere University, Finland., Christensen RD; Research Unit of General Practice, University of Southern Denmark, Institute of Public Health, Odense, Denmark., Waldstrøm M; Department of Pathology, Hvidovre Hospital, Hvidovre, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark., Lindemann K; Department of Gynecological Oncology, Oslo University Hospital, Division of Cancer Medicine, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Roed H; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Auranen A; Department of Obstetrics and Gynecology and Tays Cancer Centre, Tampere University Hospital and Tampere University, Finland., Akslen LA; Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway., Thomsen LCV; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway., Lindberg SN; Nordic Society of Gynaecological Oncology Clinical Trial Unit (NSGO-CTU), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Madsen K; Nordic Society of Gynaecological Oncology Clinical Trial Unit (NSGO-CTU), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark., Bjørge L; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Sep; Vol. 188, pp. 103-110. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1016/j.ygyno.2024.06.017
Abstrakt: Objectives: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC.
Methods: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors.
Results: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8 + cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR.
Conclusions: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.
Competing Interests: Declaration of competing interest The authors declare the following financial interest / personal relationship which may be consider as potential competing interests: MRM reports receiving an institutional study grant and investigational medicinal product from AstraZeneca (no personal grants were received). JM reports having received consulting fee payments from GlaxoSmithKline, AstraZeneca and Eisai; receiving payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Eisai; and participation on a data safety monitoring board or advisory board of Eisai. KL reports receiving research funding from GlaxoSmithKline; receiving consulting fee payments from AstraZeneca, Merck Sharp and Dohme, Nykode, Eisai and GlaxoSmithKline; and being on the safety monitoring board of Karyopharm. AA reports participation on the advisory boards of GlaxoSmithKline and Merck Sharp and Dohme. LAA reports receiving grants or contracts from the Research Council of Norway. LCVT reports receiving personal fees for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Bayer and AstraZeneca; and receiving personal fee payments from Eisai for participating on a data safety monitoring board or Advisory Board. KM reports receiving speakers' honoraria from GlaxoSmithKline and AstraZeneca; receiving compensation for travel expenses from GlaxoSmithKline and AstraZeneca; participating in a trial-specific safety review committee for Kancera AB; and being the deputy medical director for NSGO-CTU. LB reports receiving speakers' honoraria from GlaxoSmithKline, and Merck Sharp and Dohme; having leadership roles in Onkologisk Forum between 2018 and 2022, and in the NSGO and NSGO-CTU since 2021; and receiving investigational medicinal product from AstraZeneca for a researcher-initiated trial. LT, JRH, RdPC, MW, HR and SNL report no personal conflicts of interest.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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