A randomized, double-blind, placebo-controlled, phase II study to assess the efficacy and safety of farletuzumab (MORAb-003) in combination with carboplatin plus either paclitaxel or pegylated liposomal doxorubicin (PLD) in subjects with low CA125 platinum-sensitive ovarian cancer.
Year: 2016
Type: conference-abstract
Abstract: TPS5608 Background: Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor-alpha which is highly expressed in epithelial ovarian cancer (EOC) and largely absent from normal tissue. FAR potentially has anti-tumor activity via antibody dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity. A completed Phase 3 trial studied 1100 EOC subjects treated with carboplatin plus paclitaxel or docetaxel randomized in combination equally to three arms to placebo, FAR 1.25 or 2.5 mg/kg. Neither FAR dose met the study’s primary PFS endpoint. Prespecified subgroup analyses demonstrated that subjects with CA-125 ≤ 3×ULN and subjects with higher FAR exposure showed superior PFS and OS compared to placebo (JCO 2016, in press). CA125 is also implicated in the inhibition of target cell killing via ADCC by suppressing natural killer cell function, therefore higher CA125 levels may disrupt a potential FAR-mediated immune response. Based on the Phase 3 study results, a follow-on Phase 2 study in low CA125 EOC subjects using a modified FAR dosing regimen has been initiated. Methods: This global, randomized, placebo-controlled, phase 2 study (MORAb-003-011 / ENGOT-ov27 / BGOG-ov18; Clinical Trial Registry NCT02289950) will enroll approximately 210 subjects with high-grade serous EOC in platinum-sensitive first relapse. Eligible subjects must have evaluable disease and CA125 ≤ 3x ULN confirmed by central lab. Subjects will be treated at investigator discretion in a targeted 1:1 ratio to either carboplatin/paclitaxel or carboplatin/ PLD, and randomized in a 2:1 ratio to receive weekly FAR (10 mg/kg first 2 weeks followed by 5 mg/kg) or placebo. Upon completion of 6 cycles, subjects may continue on single test article maintenance until progression. Primary end point is PFS by RECIST (target HR of 0.667; 85% power; 1-sided type I error 0.10), with OS a key secondary. Thirty-four subjects are enrolled. Clinical trial information: NCT 022899950.
Source: Journal of Clinical Oncology
Institutions: University of Cincinnati, Augusta University, Imperial College London, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Saitama International Medical Center, Saitama Medical University, St. Joseph's Hospital and Medical Center, Dignity Health, University of Arizona Cancer Center, MD Anderson Cancer Center Madrid, Charité - Universitätsmedizin Berlin, Morphotek (United States), The University of Texas MD Anderson Cancer Center, Universitair Ziekenhuis Leuven
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2892380549