Hemopurifier device in patients with solid tumours who have stable or progressive disease while on a treatment that includes pembrolizumab or nivolumab: protocol for an Australian safety, feasibility and dose-finding study.

backgroundImmunotherapy with anti-programmed cell death protein 1 (anti-PD-1) inhibitors has revolutionised the treatment of many solid tumours, however, only 30-40% of patients will have a lasting clinical response. Tumour-derived extracellular vesicles (EVs) have been implicated in the spread of solid tumours and resistance to these agents. A lectin-affinity plasmapheresis device called the Hemopurifier (HP) has been developed and shown to remove EVs in vitro and in patients. We hypothesise that the treatment of patients who are not improving on a regimen that includes an anti-PD-1 agent will be safe, decrease EV concentrations and improve antitumour T cell activity.

methodsThis safety, feasibility and dose-finding study is designed in a 3+3 safety study design with three treatment cohorts. Participants who are determined not to be responding to a regimen that includes an anti-PD-1 agent will be assigned to receive either one, two or three (HP) treatments over a 1-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 Data and Safety Monitoring Board. 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 Central Adelaide Local Health Network Human Research Ethics Committee for Royal Adelaide Hospital (reference number 2024/HRE00031) and the Bellberry Human Research Ethics Committee for Pindara Private Hospital and Genesis Care/Royal North Shore Hospital (reference number 2024-06-724-A-6). The Therapeutic Goods Administration has been notified. The clinical trial is listed on the Australian New Zealand Clinical Trials Registry. Informed Consent is obtained from all participants prior to any protocol procedures being performed. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Australia New Zealand registration number ACTRN12624000732583.