Date: 2016-01-08
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in Cancer Research
Company: OncoMed Pharmaceuticals (USA - CA)
Product: rosmantuzumab - OMP-131R10 (anti-RSPO3 antibody)
Action mechanism: monoclonal antibody. R-spondin proteins bind to or activate leucine-rich repeat containing G-coupled receptors (LGRs) and blocking this activity has been shown to inhibit tumor growth. OncoMed's anti-RSPO3 (OMP-131R10) is the first drug in its class to target the R-spondin-LGR pathway. In preclinical studies OncoMed's anti-RSPO3 antibody demonstrated robust in vivo anti-tumor efficacy as a single agent and in combination with standard of care across a range of solid tumors, including colon, lung, ovarian, and pancreatic cancers, among others. The anti-RSPO3 antibody delayed tumor recurrence following termination of chemotherapy, and decreased the frequency of cancer stem cells. Anti-RSPO3 antibody represents the third product candidate in the clinic that is part of OncoMed's collaboration with Celgene.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest news: * On January 8, 2016, OncoMed Pharmaceuticals announced the publication of a manuscript in Cancer Research describing OncoMed's efforts to develop novel therapeutics against R-spondin (RSPO) targets and elucidating the link between expression of the RSPO cancer stem cell pathway and tumor growth. OncoMed is currently conducting a phase 1a/b clinical trial of its anti-RSPO3 (OMP-131R10) antibody. The article "Therapeutic Targeting of Tumor-Derived R-Spondin Attenuates beta-Catenin Signaling and Tumorigenesis in Multiple Cancer Types" (released online December 30, 2015) describes the generation of neutralizing monoclonal antibodies against RSPO-1, -2 or -3 and the successful use of these antibodies to treat diverse types of patient-derived xenografts, including colon, ovarian, pancreas and lung tumors. Of note, these anti-RSPO antibodies were effective in the tumor models regardless of whether the tumors overexpressed RSPO because of gene translocations or because of other tumor-intrinsic pathways. OncoMed is utilizing biomarker assays to prospectively screen patients for RSPO gene expression as part of its Phase 1a/b clinical program. Mechanistically, the paper establishes a functional link between RSPO expression and tumor growth. Tumor-derived RSPO can activate beta-catenin, and antibody-mediated blocking of RSPO binding to its receptor potently inhibits tumor growth. This anti-tumor activity is associated with the modulation of beta-catenin and cancer stem cell pathways.
