Study CB-839 in Combination With Nivolumab in Patients With Melanoma, ccRCC and NSCLC

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

During Phase 1, patients will be enrolled into escalating dose cohorts to determine the
recommended phase 2 dose (RP2D).

In Phase 2, patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung
cancer will be enrolled into separate cohorts.

All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

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 RECISTv1.1 criteria

- Resolution of treatment-related toxicities except alopecia

Exclusion Criteria:

- Unable to receive oral medications

- Unable to receive oral or 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, 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

- 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 HIV, Hepatitis B or C

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

- Active and/or untreated CNS disease or non-stable brain metastases