Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models

  • Cancer Sci. 2021 Jun;112(6):2467-2480. doi: 10.1111/cas.14898.
Keiji Furuuchi  1 ,  Katherine Rybinski  1 ,  James Fulmer  1 ,  Tomoyuki Moriyama  2 ,  Brian Drozdowski  1 ,  Allis Soto  1 ,  Shawn Fernando  1 ,  Kerrianne Wilson  1 ,  Andrew Milinichik  1 ,  Mary Lou Dula  1 ,  Keigo Tanaka  2 ,  Xin Cheng  1 ,  Earl Albone  1 ,  Toshimitsu Uenaka  1
Affiliations
  • 1. Epochal Precision Anti-Cancer Therapeutics (EPAT), Eisai Inc, Exton, PA, USA.
  • 2. Tsukuba Research Laboratory, Eisai, Co. Ltd, Tsukuba, Japan.
PMID: 33756060 DOI: 10.1111/cas.14898
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.

Keywords
FRA; antibody-drug conjugate; bystander effect; folate receptor alpha; serum biomarker; target engagement; triple-negative breast cancer.
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