Phase I study of MORAb-003, a humanized anti-folate receptor-alpha monoclonal antibody, in platinum resistant ovarian cancer

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5027 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 (M3) is a humanized monoclonal antibody (MAb) to FRA. Binding of M3 to FRA can prevent phosphorylation of substrates specific for the Lyn kinase; suppress proliferation of cells over-expressing FRA; mediate FRA-positive tumor cell killing via antibody-dependent cellular and complement-dependent mechanisms; and suppress tumor growth in vivo of FRA-expressing tumors in rodent xenograft models. Toxicology studies in non-human primates found no evidence of toxicity with M3 at supra-pharmacological doses. This open-label, multiple-infusion, first-in-human, dose-escalation trial evaluates the safety, pharmacokinetics (PK), and antitumor activity of M3 in patients with platinum-resistant EOC. Methods: Sequential cohorts of patients receive four weekly infusions at escalating dose levels of M3, from 12.5 mg/m2 to 100 mg/m2. Human anti-human antibody (HAHA) and PK analyses are performed. Eligible patients have EOC that relapsed < 6 months after platinum-based therapy, acceptable organ function, Karnofsky Performance Status ≥ 70%, and measurable disease by GOG-RECIST criteria. Patients undergo pulmonary function testing (PFT) at baseline, and at end of study. Results: To date, 7 women have been treated with M3: 3 at the 12.5 mg/m2 dose, 3 at 25 mg/m2, and 1 at 37.5 mg/m2. Median age was 60. Neither dose limiting toxicity nor HAHA has been observed. Grade 1 rash occurred in 1 patient. Grade 1/2 fever following drug administration occurred in 2 patients. Grade 2 FEV1 decrease was observed in a patient with likely pulmonary lymphangitic metastasis. One subject at 25 mg/m2 had radiographically stable disease. At low doses, the PK analysis demonstrated the half-life to be shorter than anticipated based on animal studies, possibly due to tumor binding. Radiolableled imaging studies are underway to determine the distribution of M3. Conclusions: The FRA-specific MAb MORAb-003 appears to be well tolerated in patients with EOC. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.