Nivolumab with or without BMS-986253 for the Treatment of Advanced Liver Cancer

Inclusion Criteria

• Have histologically confirmed evidence of hepatocellular carcinoma (HCC), Child-Pugh score of =< 7 * Participants must be willing to provide specimen from fresh, pre- and on-treatment tumor core biopsies for histologic diagnosis and translational studies
• Radiographically measurable disease by RECIST1.1 in at least one site
• Deemed to not be a candidate for resection or other local-regional therapy
• Must not be receiving treatment with other investigational agents and must not have received any other systemic therapy prior to registration * Prior radioembolization, local ablative therapies (radiofrequency, microwave or cryoablation), radiation (external beam or stereotactic), or hepatic resection permitted if completed >= 4 weeks prior to study enrollment and if patient has recovered with =< grade 1 toxicity and if untreated measurable disease is present
• Be willing and able to provide written informed consent/assent for the trial
• Have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• If hepatitis B is present, participants must be on anti-viral hepatitis B virus (HBV) therapy
• All women of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 24 hours prior to start of study treatment
• All women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment (s) and for 4 months following discontinuation of study treatment
• Male participants must not donate sperm during this period
• Absolute neutrophil count > 1000/mcL
• Platelet count > 50,000/mcL
• Hemoglobin >= 8.5 g/dL
• Total bilirubin =< 2 mg/dL or =< 1.5 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 times ULN
• International normalized ratio (INR) =< 1.5 times ULN
• Albumin >= 2.8 g/dL
• Creatinine < 2.0 mg/Dl

Exclusion Criteria

• Women who are pregnant or breastfeeding
• Presence of other malignancies. Participants with active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ * NOTE: Patients with history of malignancy are not considered to have a “currently active” malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse
• Have active or history of tuberculosis
• Participants with known human immunodeficiency virus (HIV) positive status
• Participants with known central nervous system (CNS) metastases
• Uncontrolled ascites
• Uncontrolled encephalopathy
• Uncontrolled gastro-esophageal varices
• Prior organ allograft or allogeneic bone marrow transplantation
• Participants with active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Graves disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease * Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: * Myocardial infarction or stroke/transient ischemic attack within the past 6 months * Uncontrolled angina within the past 3 months * Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) * History of other clinically significant heart disease (e.g., cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis) * Cardiovascular disease-related requirement for daily supplemental oxygen therapy
• Participants with ongoing or active, uncontrolled infections (afebrile for >= 48 hours off antibiotics). If hepatitis B is present, must be on anti-viral HBV therapy
• Must not have a psychiatric illness, other significant medical illness, or social situation which, in the investigator’s opinion, would limit compliance or ability to comply with study requirements
• Any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before
• Any uncontrolled inflammatory disease including Crohn’s disease and ulcerative colitis
• Treatment with botanical preparations (e.g., herbal supplements, including potential drugs of abuse, or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment
• Concomitant use of statins while on study
• Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
• Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and Tween 80 (polysorbate 80)
• Participants who have received a live / attenuated vaccine within 30 days of first treatment
• Concomitant use of any live / attenuated vaccine during treatment and until 100 days following last dose