Antibody‐drug conjugate MORAb‐202 exhibits long‐lasting antitumor efficacy in TNBC PDx models
Keiji Furuuchi, Katherine A. Rybinski, James Fulmer, Tomoyuki Moriyama, Brian Drozdowski, Allis Soto, Shawn Fernando, Kerrianne Wilson, Andrew Z. Milinichik, Mary Lou Dula, Keigo Tanaka, Xin Cheng, Earl F. Albone, Toshimitsu Uenaka
Abstract
The antibody-drug conjugate (ADC) MORAb-202, consisting of farletuzumab paired with a cathepsin B-cleavable linker and eribulin, targets folate receptor alpha (FRA), which is frequently overexpressed in various tumor types. MORAb-202 was highly cytotoxic to FRA-positive cells in vitro, with limited off-target killing of FRA-negative cells. Furthermore, MORAb-202 showed a clear in vitro bystander cytotoxic effect in coculture with FRA-positive/negative cells. In vivo antitumor efficacy studies of MORAb-202 were conducted with a single administration of MORAb-202 in triple-negative breast cancer (TNBC) patient-derived xenograft (PDx) models expressing low and high levels of FRA. MORAb-202 exhibited durable efficacy proportional to tumor FRA expression. Toxicology studies (Q3Wx2) in nonhuman primates suggested that the major observed toxicity of MORAb-202 is hematologic toxicity. Overall, these findings support the concept that MORAb-202 represents a promising investigational ADC for the treatment of TNBC patients.