Introduction
osteopetrosis, death, cancers
CANCERS, CHRONIC GRANULOMATOUS DISEASE, SOLID TUMORS, OSTEOPETROSIS, DISEASES
Systemic immune checkpoint blockade (ICB) with drugs targeting the programmed death one (PD-1) pathway has revolutionized oncology. ICB offers the potential for some patients to experience durable anti-tumor responses; however, the majority of patients do not respond to single-agent ICBCytokines have been used for decades as anti-cancer therapeutics with mixed success. Interferon-gamma (IFN-γ) is the only type II interferon and is FDA-approved for the treatment of two rare pediatric diseases, osteopetrosis and chronic granulomatous disease. In the 1980s-90s it was evaluated as a single agent for use against a variety of different cancers and demonstrated limited activityHere we report the results of a phase I dose escalation trial of the combination of IFN-γ and the anti-PD-1 targeted mAb nivolumab in patients with advanced solid tumors (NCT02614456). The trial establishes a recommended phase two dose of IFN-γ at 50 mcg/m