Regorafenib-pembrolizumab vs. TACE/TARE in intermediate-stage HCC beyond up-to-7.

Prior treatment

• Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
• Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications ≤ 14 days prior to randomization.

Other illness

• Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids.
• Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases.
• Cardiovascular conditions as defined within the protocol.

Lab values

• Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

Age

• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed ≤ 2 years before randomization.

Other

• No measurable tumor of a diffuse infiltrative HCC type.
• Persistent proteinuria of NCI-CTCAE v5.0 Grade 3.
• Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.
• Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes.
• Clinically meaningful ascites.

• Signed and dated Patient Informed Consent Form (PICF).
• Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures.
• Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test.
• Use of highly-effective contraceptive methods in women of CBP and men.
• Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol.
• ≥ 18 years-old at the time of PICF signature.
• Confirmed diagnosis of HCC.
• Intermediate-stage HCC, defined as follows: 1. Multinodular HCC localized to the liver, 2. No evidence of MVI or EHS, 3. Not amenable to curative treatment, 4. Child-Pugh Class A, 5. ECOG PS 0 or 1, 6. ALBI grade 1 or 2.
• Beyond up-to-seven criteria.
• Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment.
• Measurable disease by CT or MRI as per RECIST 1.1.
• No prior systemic therapy or loco-regional therapy for HCC.
• Adequate hematologic and organ function.