Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

Abstract

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-gamma) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-gamma with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-gamma. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs >= grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-gamma is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-gamma dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-gamma induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.