Nature Communications (Jul 2023)

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

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

DOI
https://doi.org/10.1038/s41467-023-40028-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 11

Abstract

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Abstract 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/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-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.