Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors

*Additional cohort specific criteria may apply

Inclusion Criteria

• Must be age 18 or older
• Ability to provide written informed consent in accordance with federal, local, and institutional guidelines
• Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life Expectancy of at least 3 months
• Adequate hepatic, renal (moderately impaired renal function in cohort 1c only), cardiac, and hematologic function
• Measurable disease by RECISTv1.1 criteria
• Resolution of treatment-related toxicities
• Willingness to avoid pregnancy or fathering children
• Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3a - 3d

Exclusion Criteria

• Currently pregnant or lactating
• Unable to receive oral medications
• Unable to receive oral or IV hydration
• Intolerance to prior anti-PD-1/PD-L1 therapy
• Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3e - 3h
• Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)
• Any other current or previous malignancy within 3 years except protocol allowed malignancies
• Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks
• Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy)
• Active known or suspected exclusionary autoimmune disease
• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks
• Concomitant therapy with valproic acid/valproate-containing therapies
• Concomitant therapy with allopurinol and other xanthine oxidase inhibitors
• History of known risks factors for bowel perforation
• Symptomatic ascites or pleural effusion
• Major surgery within 28 days before Cycle 1 Day 1
• Active infection requiring within 2 weeks prior to first dose of study drug
• Patients who have HIV, Hepatitis B or C
• Conditions that could interfere with treatment or protocol-related procedures
• Active, non-stable brain metastases or CNS disease
• Known deficiencies or suspected defect in the urea cycle
• Received live-virus vaccination within 30 days (seasonal flu vaccine allowed if non-live virus)
• NSCLC with EGFR or ALK mutation