Therasphere® and Systemic Therapy for Patients With Hepatocellular Carcinoma That is High-risk

Exclusion Criteria

• •Patients who are concurrently enrolled in another clinical study unless it is an observational (non- interventional) clinical study or the follow-up period of an interventional study.
• •Patients who are receiving any other investigational agents within 28 days of registration.
• •Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Y90, PD-1 \&PD-L1 antagonists and TKI's.
• •Note: Patients must not have a history of severe allergic reactions (i.e., Grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the systemic therapy
• •Patients must not have had prior treatment any PDL1 or PD-1 antagonists
• •Patients who have known additional malignancy that progressed or required treatment within the last 3 years. Exceptions include adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least three years.
• •Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded. These include but are not limited to patients with a history of: immune related neurologic disease
• •* multiple sclerosis
• •* autoimmune (demyelinating) neuropathy NU22I07 10.25.22 initial 19
• •* Guillain-Barre syndrome
• •* myasthenia gravis
• •* systemic autoimmune disease such as SLE
• •* connective tissue diseases
• •* scleroderma
• •* inflammatory bowel disease (IBD)
• •* Crohn's
• •* ulcerative colitis
• •* patients with a history of toxic epidermal necrolysis (TEN)
• •* Stevens-Johnson syndrome
• •* anti-phospholipid syndrome NOTE: Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• •Patients with renal failure currently requiring dialysis of any kind .
• •Patients with untreated central nervous system (CNS) metastatic disease (including spinal cord and leptomeningeal disease) are excluded.
• •Note: Subjects with previously treated CNS metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management are permitted to enroll
• •Patients receiving any concurrent chemotherapy, biologic or hormonal therapy for cancer treatment within 28 days of registration. Note: Prior cancer immunotherapy is not permitted. Note: Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
• •* Congestive heart failure \> class II NYHA.\[Appendix 4\]
• •* Unstable angina (anginal symptoms at rest) or new onset angina (began within the last 90 days )
• •* Myocardial infarction within the past 180 days.
• •Patients with cardiac ventricular arrhythmias requiring anti-arrhythmic therapy .
• •Patients having elevated lung shunting precluding treatment with Y-90.
• •Patients who have had major surgery within 4 weeks prior to registration.
• •Patients with a history of gastrointestinal bleeding (GIB) within 6 weeks prior to registration.
• •Patients with prior transplant of any kind
• •Patients who are pregnant or nursing .
• •* Hypertension that is not controlled on medication
• •* Patients who have active clinically serious infection \> CTCAEv 5 Grade 2 . Psychiatric illness/social situations that would limit compliance with study requirements
• •* Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• •* Active alcohol use, drug use, or a psychiatric disease that would, in the opinion of the PI or a sub-investigator (sub-I), prevent the subject from complying with the study protocol and/or endanger the subject during their participation in the study