Protocol for a Safety, Feasibility, and Dose-Finding Study of the Hemopurifier® Device in Patients with Solid Tumors Who Have Stable or Progressive Disease During Pembrolizumab or Nivolumab Monotherapy

ABSTRACT Background Immunotherapy with anti-PD-1 inhibitors has revolutionized the treatment of many solid tumors, however only 30-40% of patients will have a lasting clinical response. Tumor-derived extracellular vesicles (EVs) have been implicated in the spread of solid tumors and resistance to these agents. A lectin-affinity plasmapheresis device called the Hemopurifier (HP) has been developed and shown to remove extracellular vesicle in vitro and in patients. We hypothesize that the treatment of patients who are not improving on anti-PD-1 therapies will be safe, decrease EV concentrations, and improve anti-tumor T cell activity. Methods This safety, feasibility and dose finding study is designed in a 3+3 safety study design with three treatment cohorts. Participants who are determined to be not responding to anti-PD-1 monotherapy will be assigned to receive either one, two, or three (HP) treatments over a one-week period prior to their next scheduled dose of anti-PD-1 antibody. Advancement from one cohort to the next will be determined by a DSMB. Data collection will include adverse events, safety labs, EV concentrations and T cell measurements, repeat imaging and survival status. The primary outcome of the study will be the safety of the HP in this population with additional endpoints to include the kinetics of EV removal and rebound following HP treatment, in addition to the effects on T cell numbers and activity, Ethics and dissemination The clinical protocol and amendment to the study protocol have been approved by the Ethics Committees and Research Governance Offices at three participating clinical sites in Australia. The Therapeutic Good Authority (TGA) has been notified. The clinical trial is listed on the Australia New Zealand Clinical Trials Registry. Informed Consent is obtained from all participants prior to any protocol procedures being performed. Australia New Zealand Registration number ACTRN12624000732583