Interferon Gamma-1b and Nivolumab in Treating Patients with Metastatic Solid Tumors

Inclusion Criteria

• All patients must have received at least one line of systemic therapy in the metastatic setting; prior immunotherapy is allowed, including prior treatment with nivolumab, another PD-1 inhibitor, or a PD-L1 inhibitor, as long as the reason for discontinuation of a prior PD-1 pathway inhibitor was not for drug-related toxicity
• For dose escalation portion of the study: Patients must have a histologically or cytologically confirmed metastatic solid tumor that has shown clinical or pre-clinical evidence of responding to anti-PD-1 therapy or the capacity to up-regulate PD-L1; these tumor types may include but may not be limited to: renal cell carcinoma (RCC), urothelial carcinoma (UC), melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer, squamous cell cancer of the head and neck (SCCHN), ovarian carcinoma, triple negative breast cancer, gastric cancer, microsatellite instability expressing (MSI-high) colon cancer, hepatocellular carcinoma, mesothelioma, gastrointestinal stromal tumors, endometrial carcinoma, liposarcomas, chondrosarcomas, and uterine sarcomas; patients with solid tumor types not listed above may be enrolled at the discretion of the principal investigator
• For dose expansion cohorts: Dose expansion portion of study will include two separate cohorts * One cohort will incorporate patients with esophageal, gastroesophageal junction (GEJ) or gastric carcinomas (squamous cell carcinoma or adenocarcinoma if predominant histology); these patients must have received at least one prior systemic therapy for metastatic disease; patients who had prior neoadjuvant or adjuvant chemotherapy as part of curative intent primary therapy but recurred in less than 6 months would also be eligible; patients with HER2+ disease must have received trastuzumab with disease progression prior to enrollment; patients on this arm may have had prior treatment with drugs targeting the PD-1 pathway, but will be limited to a maximum of 5 patients * The second cohort will include patients who have progressed on prior PD-1 pathway inhibition (single agent or in combination) in solid tumor types where these drugs are standard of care; the reason for discontinuation of the prior PD-1 pathway drug must not have been for toxicity; eligible tumor types include melanoma, RCC, UC, NSCLC, and SCCHN, but subsequent tumor types wherein relevant agents become an approved standard of care would also become eligible
• Patients must have measurable disease per RECIST criteria version (v.) 1.1
• Patients must have a site of disease that is amenable to pretreatment and on-treatment core biopsies; at least 3 formalin fixed, paraffin embedded (FFPE) slides at five microns each may be collected at each biopsy; determination of tissue accessibility and quantity will be made by the consenting clinician; patients must consent to the two study-required biopsy procedures
• Eastern cooperative oncology group (ECOG) performance status 0 or 1
• Absolute neutrophil count > 1,500/mcL
• Platelets > 100,000/mcL
• Total bilirubin =< 1.5 times the upper normal limit (UNL), except patients with Gilbert’s syndrome in whom total bilirubin must be < 3.0 mg/dL
• Aspartate transaminase (AST)/alanine transferase (ALT) (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) < 3 times institutional normal limits
• Creatinine < 1.5 times the upper limit of normal (ULN) or creatinine clearance > 40 mL/min (as measured or calculated by Cockroft-Gault formula)
• Ability to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document

Exclusion Criteria

• Patients who have had anti-cancer systemic therapy within 2 weeks prior to entering the study; radiation is allowed
• Patients may not have any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids or immunosuppressive medications, except for syndromes which would not be expected to recur in the absence of an external trigger; subjects with vitiligo, type I diabetes mellitus, or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to first dose of study drug; inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease
• Patients may not be receiving any other investigational agents
• Patients with known active or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis; asymptomatic, treated, and/or stable brain metastases, as measured by subsequent radiologic evaluations at least two months apart, are permitted
• History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
• Known human immunodeficiency virus (HIV) positive or history of acquired immune deficiency syndrome (AIDS) or AIDS-defining illness
• Known current or a history of hepatitis B or C virus, including chronic and dormant states, unless disease has been treated and confirmed cleared
• Any medical condition that in the investigator’s opinion could interfere with interpretation of study or toxicity, or increase the risk to the patient related to potential toxicity
• Major surgery within 4 weeks of initiation of study drug
• Pregnant or breast feeding
• A second invasive malignancy requiring active treatment