APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion

This phase randomized phase 2 clinical trial to study the safety and effect of C3 complement inhibitor APL-2 (Pegcetacoplan) alone and in combination with Pembrolizumab, as well as APL-2 in combination with both Bevacizumab and Pembrolizumab in patients with recurrent ovarian, fallopian tube or primary peritoneal cancer with symptomatic malignant effusion (ascites or pleural effusion). APL-2 (Pegcetacoplan) is the lead drug in the class of compstatins, which are synthetic peptides that bind to C3 and inhibit the classical and alternative pathway C3 convertase formation required for complement activation. The rationale for using APL-2 in recurrent ovarian, fallopian tube and primary peritoneal cancer with recurrent malignant effusion is two-fold: (1) to decrease the immune system suppressing neutrophil cell accumulation in tumor tissue thereby making immune check point blockade more effective; and (2) to prevent generation of anaphylatoxins (C3a, C4a, and C5a) that increase vessel permeability and lead to malignant fluid accumulation. The current standard for palliation of ascites and/or pleural effusions in recurrent ovarian/fallopian tube/primary peritoneal cancer involves the use of bevacizumab alone or combined with a chemotherapy drug as well as repeated drainage of the fluid.

Randomized Phase 2 Trial of APL-2 with Pembrolizumab vs. APL-2 with Pembrolizumab and Bevacizumab vs. Bevacizumab alone in Patients with Recurrent Ovarian Cancer and Persistent Malignant Effusion