Abstract 1760: Preclinical evaluation of IMGN853, an anti-FOLR1 antibody-maytansinoid conjugate, as a potential therapeutic for ovarian cancer

IMGN853 (M9346A-sulfo-SPDB-DM4) is an antibody drug-conjugate consisting of the cytotoxic maytansinoid, DM4, covalently linked to the humanized monoclonal antibody M9346A, which selectively binds to folate receptor 1 (FOLR1). FOLR1 is over-expressed on ovarian cancers (38 of 67 tumor samples positive for FOLR1 ∼ 57%) suggesting that ovarian cancer may be a primary indication for clinical development of IMGN853. FOLR1 expression was evaluated on a panel of ovarian cancer xenografts and human ovarian tumors using a calibrated immunohistochemical (IHC) staining method on formalin-fixed paraffin-embedded sections. The FOLR1 expression levels and patterns in three ovarian adenocarcinoma xenografts, OVCAR-3, IGROV-1 and OV-90, were consistent with those observed in FOLR1-positive patient ovarian tumor samples. The anti-tumor activity of IMGN853 was evaluated in the three FOLR1-positive ovarian xenograft models identified. CB.17 SCID mice bearing established subcutaneous xenograft tumors (approximately 100 mm3) were treated with a single intravenous injection of IMGN853 at 1.2, 2.5 and 5.0 mg/kg (based on antibody concentration). IMGN853 was active in all three models evaluated. In OVCAR-3 xenografts, the minimally efficacious dose (MED) of IMGN853 was 1.2 mg/kg. The higher dose levels were highly active, resulting in complete regressions (CR) in 4/6 and 6/6 mice in the 2.5 and 5.0 mg/kg treatment groups, respectively. Treatment with IMGN853 resulted in strong anti-tumor activity in both IGROV-1 and OV-90 xenograft models, with a MED of 2.5 mg/kg, single injection. The strong anti-tumor activity of IMGN853 against ovarian xenograft tumors with FOLR1 expression levels comparable to patient tumors suggests that IMGN853 may be a promising candidate for clinical development in ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1760. doi:10.1158/1538-7445.AM2011-1760