A late-phase randomized open-label multi-cohort trial to evaluate immune-related adverse events with different standard-of-care dosing strategies of standard-of-care immunotherapies: ImmuRAd trial.

Abstract

TPS12172 Background: Programmed cell death-1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, are widely used in treating solid tumors. These inhibitors have multiple FDA-approved dosing schedules. Extended-interval, higher-dose regimens offer patient convenience and health-system efficiencies. However, there is limited comparative prospective data evaluating immune-related adverse events (irAEs) across different dosing strategies. Our study aims to evaluate this important safety question in routine clinical practice. Methods: ImmuRAd is an investigator-initiated, open-label, randomized late phase trial. Adults (≥18 years) with histologically or cytologically confirmed solid tumor malignancies who are scheduled to receive standard-of-care PD-1 inhibitor-based therapy in any disease setting or line of therapy are eligible for the study. Participants are randomly assigned to one of two pre-defined standard dosing strategies based on their physician-selected PD-1 inhibitor cohort. In the nivolumab cohort, patients are randomized 1:1 to receive nivolumab 240 mg every 2 weeks or nivolumab 480 mg every 4 weeks. In the pembrolizumab cohort, patients are randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks or pembrolizumab 400 mg every 6 weeks. Route of administration is at the discretion of the investigator and can be given intravenous or subcutaneous. After completing 12 weeks of therapy, patients meeting predefined treatment-tolerance criteria may transition to extended-interval dosing at the discretion of the treating investigator. The primary objective is to determine the proportion of patients experiencing grade ≥3 immune-related adverse events (CTCAE v5.0) in each dosing arm within each cohort. Secondary endpoints include the incidence of all-grade immune-related adverse events, the time to resolution of these adverse events, treatment discontinuation due to immune-related adverse events, the overall response rate (for patients with measurable disease), progression-free or disease-free survival, and overall survival. Exploratory analyses will investigate the associations between immune-related adverse events and factors such as tumor type, treatment setting, microsatellite instability status, tumor mutational burden, and NGS biomarker profiles. The planned sample size is 192 evaluable patients (96 per cohort and 48 per arm). The study will enroll patients over a period of 24 months and will have a follow-up period of up to 2 years. In this IRB approved clinical trial, safety oversight will be provided by the institutional Data Safety Monitoring Committee. Trial Status: The study is actively enrolling at The University of Kansas Cancer Center and affiliated network sites. Clinical trial information: NCT07174453 .