A Phase 1/2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Glutaminase Inhibitor CB-839 in Combination with Nivolumab in Patients with Advanced/Metastatic Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer

This study is an open-label Phase 1/2 evaluation of CB-839 in combination with nivolumab in
participants with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

Addition eligibility criteria based on tumor type apply

Inclusion Criteria:

- 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, cardiac, and hematologic function

- Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
criteria

- Resolution of treatment-related toxicities except alopecia

Exclusion Criteria:

- Unable to receive oral medications

- Unable to receive oral or intravenous (IV) hydration

- Intolerance to prior anti-PD-1/PD-L1 therapy

- Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)

- Any other current or previous malignancy within 3 years except protocol allowed
malignancies

- Chemotherapy, TKI 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

- 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 parenteral antibiotics, antivirals, or antifungals within 2
weeks prior to first dose of study drug

- Patients who have human immunodeficiency virus (HIV), Hepatitis B or C

- Conditions that could interfere with treatment or protocol-related procedures

- Active and/or untreated central nervous system (CNS) disease or non-stable brain
metastases