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dc.contributor.authorKyte, J. A
dc.contributor.authorAndresen, N. K
dc.contributor.authorRussnes, H. G
dc.contributor.authorFretland, S. Ø
dc.contributor.authorFalk, R. S
dc.contributor.authorLingjærde, O. C
dc.contributor.authorNaume, B.
dc.date.accessioned2020-07-07T06:43:13Z
dc.date.available2020-07-07T06:43:13Z
dc.date.issued2020
dc.identifier.citationJournal of Translational Medicine. 2020 Jul 03;18(1):269
dc.identifier.urihttp://hdl.handle.net/10852/77569
dc.description.abstractBackground Immunotherapy with checkpoint inhibitors (CPI) targeting PD-1 or CTLA-4 has emerged as an important treatment modality for several cancer forms. In hormone receptor positive breast cancer (HR + BC), this therapeutic approach is largely unexplored. We have started a clinical trial, ICON (CA209-9FN), evaluating CPI combined with selected chemotherapy in patients with metastatic HR + BC. The tumor lymphocyte infiltration is predictive for the effect of chemotherapy in BC. In ICON, we use anthracycline, which are considered as “immunogenic” chemotherapy, and low-dose cyclophosphamide, which has been reported to counter immunosuppressive cells. Methods ICON is a randomized exploratory phase IIb study evaluating the safety and efficacy of combining nivolumab (nivo; anti-PD-1) and ipilimumab (ipi; anti-CTLA-4) with chemotherapy in subjects with metastatic HR + BC. Primary objectives are aassessment of toxicity and progression-free survival. The trial will enrol 75 evaluable subjects, randomized 2:3 into two arms (A:B). Patients in Arm A receive only chemotherapy, i.e. pegylated liposomal doxorubicin (PLD 20 mg/m2 intravenously every 2nd week) + cyclophosphamide (cyclo; 50 mg per day, first 2 weeks in each 4 week cycle). Patients in Arm B receive PLD + cyclo + ipilimumab (1 mg intravenously every 6th week) + nivolumab (240 mg intravenously every 2nd week). Patients in arm A will be offered ipi + nivo after disease progression. Discussion ICON is among the first clinical trials combining chemotherapy with PD-1 and CTLA-4 blockade, and the first in BC. There is a strong preclinical rationale for exploring if anthracyclines, which are considered to induce immunogenic cell death, synergize with CPI, and for combining PD-1 and CTLA-4 blockade, as these checkpoints are important in different phases of the immune response. If the ICON trial suggests acceptable safety and provide a signal of clinical efficacy, further studies are warranted. The cross-over patients from Arm A receiving ipilimumab/nivolumab without concomitant chemotherapy represent the first BC cohort receiving this therapy. The ICON trial includes a series of translational sub-projects addressing clinically important knowledge gaps. These studies may uncover biomarkers or mechanisms of efficacy and resistance, thereby informing the development of novel combinatory regimes and of personalised biomarker-based therapy. Trial registration NCT03409198, Jan 24th 2018; https://clinicaltrials.gov/ct2/show/record/NCT03409198
dc.language.isoeng
dc.rightsThe Author(s); licensee BioMed Central Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleICON: a randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer
dc.typeJournal article
dc.date.updated2020-07-07T06:43:14Z
dc.creator.authorKyte, J. A
dc.creator.authorAndresen, N. K
dc.creator.authorRussnes, H. G
dc.creator.authorFretland, S. Ø
dc.creator.authorFalk, R. S
dc.creator.authorLingjærde, O. C
dc.creator.authorNaume, B.
dc.identifier.cristin1877616
dc.identifier.doihttps://doi.org/10.1186/s12967-020-02421-w
dc.identifier.urnURN:NBN:no-80674
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/77569/1/12967_2020_Article_2421.pdf
dc.type.versionPublishedVersion
cristin.articleid269


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