Farletuzumab ecteribulin

Farletuzumab ecteribulin (MORAb-202) is an antibody-drug conjugate (ADC), consisting of the humanized anti-human folate receptor alpha (FRA) antibody Farletuzumab (HY-P99153) conjugated via reduced interchain disulfide bonds to Mal-PEG2-Val-Cit-PAB-eribulin. Farletuzumab ecteribulin has a drug-to-antibody ratio of 4.0. Farletuzumab ecteribulin is highly cytotoxic to FRA-positive cells in vitro. Farletuzumab ecteribulin has potent antitumor activity[1][2].

Research Areas >> Cancer

Farletuzumab ecteribulin (MORAb-202; 5.1 pM-10 μM; 5 天) 在体外对 FRA 阳性细胞具有高度细胞毒性 (IGROV-1: IC50=1 nM, NCI-H2110: IC50=74 nM, A431-A3: IC50=2.3 μM)[1]。 Cell Cytotoxicity Assay[1] Cell Line: Human IGROV-1, OVCAR3-A1, NCI-H2110, A431-A3, and SJSA-1 cells Concentration: 5.1 pM-10 μM Incubation Time: 5 days Result: MORAb-202 showed potent cytotoxicity against IGROV-1 (IC50=1 nM), NCI-H2110 (IC50=74 nM), and A431-A3 (IC50=2.3 μM). Exhibited little killing activity against the FRA-negative cell line SJSA-1 (IC50>10 μM).

Farletuzumab ecteribulin (MORAb-202; 静脉给药; 第 0 天单次注射 1, 5 mg/kg; 或每 11 天注射一次 5 mg/kg, 共2次; 60 天) 在一次或两次 5 mg/kg剂量下具有显着的抗肿瘤活性[1]。 Farletuzumab ecteribulin (2mg/kg; 静脉给药) 第 1 天在雄性和雌性食蟹猴中的 T1/2 分别为 192 和 162 小时，AUC(0-t) 分别为 7160 和 6300 ug·h/m[1]。 Animal Model: Female SWISS nude mice with triple-negative breast cancer (TNBC) patient-derived xenograft (PDx) model (OD-BRE-0631)[1]. Dosage: 1, 5 mg/kg Administration: IV; single injection 1, 5 mg/kg at day 0 ((Q1Dx1) or 5 mg/kg every 11 days (Q11Dx2)); 60 days Result: A significant antitumor activity was observed in mice treated once or twice 5 mg/kg, while no antitumor activity compared with vehicle group was observed in mice treated with 1 mg/kg. Animal Model: Male and female cynomolgus monkeys[1]. Dosage: 2mg/kg (Pharmacokinetic Analysis) Administration: IV Result: Had a T1/2s of 192 and 162 hours and AUC(0-t)s of 7160 and 6300 ug·h/mfor male and female cynomolgus monkeys on Day 1.

[1]. Keiji Furuuchi, et al. Antibody-drug conjugate MORAb-202 exhibits long-lasting antitumor efficacy in TNBC PDx models. Cancer Sci. 2021 Jun;112(6):2467-2480.  

[2]. Xin Cheng, et al. MORAb-202, an Antibody-Drug Conjugate Utilizing Humanized Anti-human FRα Farletuzumab and the Microtubule-targeting Agent Eribulin, has Potent Antitumor Activity. Mol Cancer Ther. 2018 Dec;17(12):2665-2675.