IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC)

Inclusion Criteria

• Histologically confirmed diagnosis of HCC
• Has a Child-Pugh Classification score ≤ 6 for assessed liver function within 7 days before allocation (Appendix 4: Child-Pugh Score)
• Candidate for local ablation (via either RFA or MWA or brachytherapy or combination of TACE with RFA, MWA or brachytherapy [ablation technique according to Investigator's choice]), i.e.:

According to Investigator's assessment an R0 state can be obtained after a maximum of two RFA/MWA interventions (initial ablation + one additional re-ablation at maximum).

• Patients (including high risk patients) with: :
• Presence of ≤ 5 tumor nodules with diameters ≤ 7cm [longest axis] each OR
• Vascular infiltration
• Has received no prior systemic therapy for HCC NOTE: Patients who have received prior local therapy by transarterial chemoembolization (TACE) are not excluded if TACE has been performed >8 weeks before study allocation.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously treated (e.g. irradiated or subject to TACE) area are considered measurable if vital tumor has been demonstrated by contrast enhanced imaging in such lesions*.
• Male/female participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study.
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.

A male participant with female partner of childbearing potential is eligible to participate if he agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.

• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have provided archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated for mandatory pre-treatment evaluation (baseline).
• Newly obtained biopsies are preferred to archived tissue (archived specimen ≤6 months may be acceptable).
• Core or excisional biopsies mandatory (fine needle aspiration and bone metastasis samples are not acceptable).
• Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
• If submitting unstained cut slides, newly cut slides should be submitted to the central pathology lab within 14 days from the date slides are cut.
• Availability of baseline tumor biopsy samples has to be ensured by site before first dose of study medication is administered.
• Specimens have to be sent to central pathology lab for accompanying research project.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
• Have adequate organ function as defined in the following table. Specimens must be collected within 7 days prior to the start of study treatment.

Adequate Organ Function Laboratory Values

Hematological

• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L(a)

Renal

• Creatinine OR ≤1.5 × Upper Limit of Normal (ULN) OR Measured or calculated(b) creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN

Hepatic

• Total bilirubin ≤2.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >2.5 × ULN
• aspartate aminotransferase [AST (SGOT)] and alanine aminotransferase [ALT (SGPT)] ≤5 × ULN

Coagulation

• International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT