Randomized phase II trial of pegylated liposomal doxorubicin (PLD) with or without anti-platelet-derived growth factor receptor-alpha (PDGFR-alpha) monoclonal antibody IMC-3G3 in platinum-refractory/resistant advanced ovarian cancer.

TPS256 Background: Single-agent PLD is an established therapy for platinum-refractory/resistant advanced ovarian cancer with response rates of approximately 20%. This ongoing study will assess antitumor activity and safety of PLD with or without IMC-3G3 in this population. IMC- 3G3 is an IgG1-type recombinant human monoclonal antibody which specifically targets PDGFRα with high affinity, blocks ligand-induced cell mitogenesis and receptor autophosphorylation, and inhibits phosphorylation of the downstream signaling molecules Akt and MAP kinase (Mol Cancer Ther 2005;4:369). PDGFRα is expressed in 52% of ovarian cancers, including in 89% with clear cell histology (Oncogene. 2002;21:6289). PDGF and PDGFRα are often co-expressed in ovarian cancers, suggesting an autocrine mechanism of tumor growth, and PDGFRα expression is associated with shorter survival in patients (Ca Res 1993; 53: 4550). Ovarian cancer-associated ascites fluid contains PDGF, and can stimulate ovarian cancer growth through PDGFRα signaling...