TREMELIMUMAB-ACTL INJ,SOLN

Clinical Criteria Summary

Unresectable hepatocellular carcinoma (uHCC)
First-line (1L) setting
Patients who are not candidates for atezolizumab and bevacizumab
Candidates for immune checkpoint inhibitor (ICI) therapy but not candidates for bevacizumab

Combination with durvalumab: Cycle 1, day 1 dosing followed by durvalumab monotherapy every 4 weeks
Patients >30 kg: Tremelimumab 300 mg x 1 with durvalumab 1500 mg on Cycle 1, day 1
Patients <30 kg: Tremelimumab 4 mg/kg x 1 with durvalumab 20 mg/kg on Cycle 1, day 1

AASLD Clinical Practice Guideline 2023: Listed as a 1L option in non-VEGF candidates (i.e., bevacizumab)
National VA Clinical Gastrointestinal Pathway 2023: Listed as a 1L option in HCC for ICI candidates who are not candidates for bevacizumab
NCCN Guidelines Version 2.2023: Listed as a preferred 1L systemic therapy (category 1)

Monitor for early identification and management of immune-mediated adverse reactions impacting any organ or tissue (e.g., pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, pancreatitis)
Evaluate appropriate labs; withhold or discontinue based on severity and type of reaction
Interrupt, reduce rate, or permanently discontinue for infusion-related reactions based upon severity
Avoid corticosteroids at therapy initiation as they may lessen therapeutic effect (though corticosteroids may be required to treat immune-mediated AEs)

Diagnosis of hepatocellular carcinoma
No prior systemic therapy for Hepatocellular carcinoma (HCC), unless prior regimen discontinued premature due to intolerance
Not a candidate to receive bevacizumab, therefore atezolizumab/bevacizumab regimen is not a 1L option
Patient is able to receive durvalumab, in combination with tremelimumab
Barcelona Clinic Liver Cancer stage B (not eligible for locoregional therapy) or stage C
Child-Pugh score Class A

Eastern Cooperative Oncology Group Performance Status 0 or 1
Goals of care and role of Palliative Care Consult has been discussed and documented

Autoimmune disease
Immunosuppression including corticosteroid equivalent greater than 10 mg per day of prednisone
Primary immunodeficiency
History of allogeneic organ transplantation
Untreated brain metastases
Ascites requiring non-pharmacologic intervention in prior 6 weeks
Hepatic encephalopathy in prior 12 months
Uncontrolled systemic infection, including hepatitis B or C or known HIV
Pregnancy
Lactating

For patients who can become pregnant: Pregnancy must be excluded prior to receiving tremelimumab.
For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for three months after stopping treatment.