Journal Article

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

Geynisman, Daniel M., Zibelman, Matthew, Dotan, Efrat, Dulaimi, Essel Al-Saleem, Kokate, Rutika, MacFarlane, Alexander W., Costello, Kimberly, Borghaei, Hossein, Alpaugh, R. Katherine, O’Neill, John, Ruth, Karen, Devarajan, Karthik, Denlinger, Crystal S., McGowan, Thomas, Cukierman, Edna, Martin, Lainie, Obeid, Elias, Campbell, Kerry S., Einarson, Margret, Jain, Angela, Plimack, Elizabeth R.

2023

Overview

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ 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-γ. 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-γ is 75 mcg/m 2 , however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m 2 . 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-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456. The majority of cancer patients do not respond to single agent immune checkpoint blockade and several combinatorial approaches have now been tested. Here the authors report the results of a phase I dose escalation trial of nivolumab (anti-PD1) in combination with IFN-γ in patients with advanced solid tumors.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/21 / 13/31 / 13/51 / 692/4028/67/1059/2325 / 692/4028/67/1059/2326 / Adverse events / Chemokines / Combinatorial analysis / Corticoids / Corticosteroids / Humanities and Social Sciences / Immune checkpoint inhibitors / Immune system / Immunotherapy / Interferon / Metastases / Monoclonal antibodies / Monocytes / multidisciplinary / Patients / PD-1 protein / PD-L1 protein / Safety / Science / Science (multidisciplinary) / Solid tumors / Targeted cancer therapy / Tumors / γ-Interferon