Farletuzumab is an investigational humanized IgG1 antibody targeting folate receptor alpha (FRA), which is highly expressed in epithelial cancers, such as ovarian, endometrial, breast, renal, lung, colorectal and pituitary, but is mostly absent from normal tissue. The antibody received orphan drug designation for ovarian cancer in the US, EU and Switzerland.
Farletuzumab is a monoclonal antibody being developed for its potential treatment of ovarian and lung cancers. A Phase 1 study (NCT00428766) was conducted at Memorial Sloan Kettering Cancer Center in patients with refractory ovarian cancer. A multi-institutional Phase 2 study (NCT00318370) of farletuzumab in combination with carboplatin and a taxane was performed in platinum-sensitive ovarian cancer to test the regimen’s safety and ability to improve clinical outcomes.
Based on the Phase 2 study results, Morphotek conducted a global, randomized, double-blind, placebo-controlled Phase 3 study (NCT00849667), MORAb-003-004 (also known as FAR-131). MORAb-003-004 investigated the safety and efficacy of weekly farletuzumab in combination with a platinum standard chemotherapy regimen (carboplatin plus taxane) in platinum-sensitive ovarian cancer patients in first relapse.
All MORAb-003-004 subjects received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomized test product 1:1:1 farletuzumab 1.25 mg/kg, farletuzumab 2.5 mg/kg, or placebo), and single-agent test product was continued weekly until disease progression. Neither farletuzumab dose met the study’s primary progression-free survival (PFS) endpoint when compared to placebo, with PFS of 9.0, 9.5 (hazard ratio [HR] = 0.99) and 9.7 months (HR = 0.86) for the placebo, farletuzumab 1.25 mg/kg, and farletuzumab 2.5 mg/kg arms, respectively. There was no difference in overall survival. Prespecified subgroup analyses demonstrated that subjects with a low CA125 level (less than three times the upper limit of normal) correlated with longer PFS (HR=0.49) and OS (HR=0.44) for farletuzumab 2.5 mg/kg versus placebo. Subjects with higher farletuzumab exposure also showed superior PFS and OS compared to placebo. CA125 is a tumor-produced protein elevated in the blood of some ovarian cancer patients that has been previously reported to reduce natural killer (NK) cell function; therefore, higher CA125 levels may interfere with the immune response associated with farletuzumab’s potential activity.
The most common adverse events were those known to be associated with chemotherapy, including: alopecia; nausea; neutropenia; fatigue; thrombocytopenia; and neuropathy.
Based on the encouraging results from the prespecified subgroup analyses, Morphotek initiated a Phase 2 trial (NCT02289950), MORAb-003-011, in March 2015 to further investigate the potential clinical benefit observed in the MORAb-003-004 patients with a low CA125 level. This global study will assess the safety and efficacy of farletuzumab, using a modified dosing schedule guided by exposure-response analysis from the Phase 3 study, in combination with a platinum doublet in first-relapsed, platinum-sensitive ovarian cancer patients with low CA125 blood levels. Morphotek expects to enroll 210 patients in this study, which will be conducted in sites across the United States, Japan, and Europe.
FRA has been found to be expressed at varying degrees in non-small cell lung adenocarcinoma. To evaluate the effects of farletuzumab in patients with varying degrees of FRA expression, a randomized, double-blind, placebo-controlled Phase 2 study (NCT01218516) was performed to determine if farletuzumab delays the time to tumor progression when added to one of the standard-of-care chemotherapy options for metastatic adenocarcinoma of the lung. Secondary objectives included safety, response rate, duration of response, and overall survival benefit in patients treated with the antibody plus chemotherapy versus the chemotherapy with a placebo.
The information contained herein is investigational and is not intended to make claims of safety or efficacy prior to approval by the FDA or other regulatory authorities. There is no guarantee that the agents described or their uses will be approved by the FDA or other regulatory authorities.