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, andinstitutional guidelines

• Histological or cytological diagnosis of metastatic cancer or locally advancedcancer 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 allowedmalignancies

• Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonaltherapy 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 mgdaily 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 ifnon-live virus)

• NSCLC with EGFR or ALK mutation