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Safety and efficacy of a DKK1 inhibitor (DKN-01) in combination with pembrolizumab (P) in patients (Pts) with advanced gastroesophageal (GE) malignancies

Year: 2018
Type: article
Abstract: Background: Dickkopf-1 (DKK1) is a modulator of the Wnt and PI3K/AKT signaling pathways and contributes to an immunosuppressive tumor microenvironment by activating MDSCs and Tregs. DKN-01 (D), an mAb against DKK1, acts on innate immune cells, and in preclinical studies demonstrates upregulation of both PD-L1 and IFNγ-related chemokines, suggesting a role for immune checkpoint combination. Anti-PD-1 plus DKN-01 shows additive antitumor effects in the B16 syngeneic mouse model; clinical studies are underway.
DOI: 10.1093/annonc/mdy282.044
Authors: S.J. Klempner, J. Bendell, V. Meucci Villaflor, L. Tenner, S. Stein, C.A. Sirard, W. Newman, M. Kagey, K. Schlienger, J. Strickler
Institutions: Angeles Clinic and Research Institute, Tennessee Oncology, Northwestern University, The University of Texas at San Antonio Health Science Center, Yale University, Leap Therapeutics, Inc. (United States), Merck & Co., Inc., Rahway, NJ, USA (United States), Duke Medical Center
Language: English
Subfield: Oncology
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $5,080
OpenAlex ID: W2898288568
FWCI: 0.945
Cites:
Cited by: 13
Related to: 10