A Phase 3, Double-Blind, Placebo-Controlled, Multicenter Clinical Study comparing Chemo-Immunotherapy (Paclitaxel-Carboplatin-Oregovomab) versus Chemotherapy (Paclitaxel-Carboplatin-Placebo) in Patients with Advanced Epithelial Ovar

QPT-ORE-005 is a Phase 3 study designed to confirm the promising results of the Phase 2 study QPT-ORE-002 (Ferrandina 2017). As shown in QPT-ORE-002, adding oregovomab (MAb-B43.13), to a standard regimen of paclitaxel and carboplatin to treat patients with frontline ovarian and associated cancers after optimal debulking surgery, resulted in clinically significant improvements in outcomes with little additional toxicity. In QPT-ORE-002, a total of 97 subjects, with previously untreated, advanced Stage III or IV, epithelial ovarian, adnexal, or peritoneal cancer, were treated after undergoing optimal debulking surgery (residual disease < 1 cm in diameter) and followed for 3 years after treatment. Subjects treated with oregovomab + paclitaxel/carboplatin had a clinically significant improved PFS (median 41.8 months) compared to paclitaxel/carboplatin alone (median 12.2 months) by the K-M method (p=0.0027) and a HR=0.44 by multivariate Cox PH method (p=0.0029). The subjects treated with oregovomab + paclitaxel/carboplatin also had a clinically significant improved OS (median NE) compared to paclitaxel/carboplatin alone (median 43.2 months) by the K-M method (p=0.0042) and a HR=0.34 by the multivariate Cox PH method (p=0.0077), as well as a clinically significant improved time to clinical progression (TTCP) (median 43.1 months) compared to paclitaxel/carboplatin (median 13.6 months) by the K-M method (p=0.0014) and a HR=0.40 by the multivariate Cox PH method (p=0.0019). Subjects treated with oregovomab + paclitaxel/carboplatin had no clinically significant additional safety or adverse event issues compared to paclitaxel/carboplatin alone. Study QPT-ORE-005 is designed to confirm the clinical safety and efficacy results seen in the Phase 2 study (QPT-ORE- 002) described above. Rationale for 2 mg dose of oregovomab: Oregovomab has a unique mechanism of action (MOA) based on immunological stimulation following its binding to CA- 125, which is highly expressed in the target tumor and also present in the circulating plasma. Current evidence supports that this binding in vivo renders the target antigen CA-125 more immunogenic or gneoantigen-likeh through altered and enhanced antigen processing and presentation to specific T cells. This induces antigen-antibody uptake and processing via pathways, notably including the immunoglobulin FcƒÁ binding via the mannose receptor, FcƒÁR1, and CCR5, a binding pattern in the human unique to murine IgG1. This results in cross presentation of CA-125 peptides and initiation of local specific immune responses with an IFN-ƒÁ signature. These properties initiate demonstrable humoral and cellular responses in patients with CA-125-positive cancer who are otherwise in a state of relative immune tolerance to their disease. The activity is clinically enhanced when oregovomab is given in combination with selected chemotherapy administered in a specific schedule to patients with Stage III or IV epithelial ovarian, fallopian tube, or peritoneal cancer in the front-line setting, after optimal debulking surgery (residual disease . 1 cm).