Abstract B115: MORAb-202: a folate receptor alpha (FRA)-targeting antibody-drug conjugate, exhibiting targeted antitumor activity and bystander elimination of cancer-associated fibroblasts

• Published in: Molecular cancer therapeutics 2018-01, Vol.17 (1_Supplement), p.B115-B115
• Main Authors: Rybinski, Katherine A., Maddage, Christopher, Cheng, Xin, Albone, Earl, Grasso, Luigi, Furuuchi, Keiji, Uenaka, Toshimitsu
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-17-B115

Triple-negative breast cancer (TNBC) is a highly metastatic disease with very poor long-term prognosis. Because of the lack of well-defined molecular targets, traditional chemotherapy is currently the only therapeutic regimen for TNBC. Within this agent class, eribulin has been approved for metastatic breast cancer and the prespecified subgroup analysis in phase 3 clinical trial (study301) revealed that eribulin demonstrated the greatest therapeutic benefit on overall survival of TNBC patients among all other breast cancer subtypes. Folate receptor alpha (FRA) is a GPI-linked membrane glycoprotein that has limited expression in normal tissue, but is highly overexpressed on a large number of cancers of epithelial origin, including non-small cell lung cancer (NSCLC), ovarian cancer, and TNBC. These features make FRA an attractive target for the treatment of TNBC using targeted therapeutic approaches. Farletuzumab, a humanized monoclonal antibody targeting FRA, has been investigated in multiple clinical trials enrolling patients overexpressing FRA. MORAb-202, a novel antibody-drug conjugate (ADC) consisting of farletuzumab conjugated to eribulin, targets FRA overexpressed by a variety of tumor types including TNBC. Upon binding and internalization, it is hypothesized that the liberated eribulin elicits both a direct cytotoxic effect on FRA-positive tumor cells and a bystander effect on FRA-negative tumor cells and, importantly, tumor-associated stromal cells within the tumor microenvironment. To address this hypothesis, we have evaluated the in vivo efficacy of MORAb-202 against a FRA-positive TNBC patient-derived xenograft (PDX) model. Single administration of 5 mg/kg MORAb-202 mediated tumor regression statistically compared to vehicle control (P