Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Arginase Inhibitor INCB001158 (formerly known as CB- 1158) as a Single Agent and in Combination with Immune Checkpoint Therapy in Patients with Advanced/Metastatic Solid Tumors

This study is an open-label Phase 1/Phase 2 evaluation of 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