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- Title
A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.
- Authors
Zibelman, Matthew; MacFarlane IV, Alexander W.; Costello, Kimberly; McGowan, Thomas; O'Neill, John; Kokate, Rutika; Borghaei, Hossein; Denlinger, Crystal S.; Dotan, Efrat; Geynisman, Daniel M.; Jain, Angela; Martin, Lainie; Obeid, Elias; Devarajan, Karthik; Ruth, Karen; Alpaugh, R. Katherine; Dulaimi, Essel Al-Saleem; Cukierman, Edna; Einarson, Margret; Campbell, Kerry S.
- 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. 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.
- Subjects
NIVOLUMAB; CD14 antigen; INTERFERON gamma; IMMUNE checkpoint proteins; PROGRAMMED cell death 1 receptors; CANCER patients; TREATMENT duration
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40028-z