Trial Outcomes & Findings for IMMULAB - Immunotherapy With Pembrolizumab in Combination With Local Ablation in Hepatocellular Carcinoma (HCC) (NCT NCT03753659)

Race and Ethnicity were not collected from any participant.

Evaluation of ORR according to RECIST 1.1 after two cycles of pembrolizumab and before performing local ablation will allow testing of the hypothesis that pre-interventional treatment with pembrolizumab before local ablation will result in conversion / downstaging of borderline candidates for local ablation. Furthermore, ORR is generally accepted as a valid endpoint for efficacy evaluation in one-armed trials without control group. Criteria used for this Outcome Measure: Percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target and non-target lesions assessed by radiological imaging: Complete Response (CR): Disappearance of all lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions and no new non-target lesions and no progression in non-target-lesions. Overall Response (OR) = CR + PR.

TTR has meanwhile been accepted by medicinal agencies in drug approval processes as they allow for quicker efficacy assessment. This is most important in explorative clinical trials in early phases (like this phase II trial) as it allows for more rapid evaluation of the potential of new treatment approaches. Furthermore, many of these parameters are not influenced by follow-up therapies. Criteria used for this Outcome Measure: Length of time after performance of local ablation resulting in confirmed absence of viable tumor tissue until documented tumor recurrence (appearance of one or more new lesion(s)).

Recurrence free survival hasmeanwhile been accepted by medicinal agencies in drug approval processes as they allow for quicker efficacy assessment. This is most important in explorative clinical trials in early phases (like this phase II trial) as it allows for more rapid evaluation of the potential of new treatment approaches. Furthermore, many of these parameters are not influenced by follow-up therapies. Criteria used for this Outcome Measure: Length of time after performance of local ablation resulting in confirmed absence of viable tumor tissue until documented tumor recurrence (appearance of one or more new lesion(s)) or death due to any cause.

Overall survival will be evaluated and is still considered the gold standard for efficacy evaluation in clinical trials. Its major drawback is the potentially long observation period necessary for OS evaluation - especially in the curative setting as represented by the treatment approach in this trial. Criteria used for this Outcome Measure: Time from allocation to the date of death of any cause.

Incidence and severity of adverse events according to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Criteria used for this Outcome Measure: Adverse events were recorded and graded according to version 4.03 of National Cancer Institute Common Toxicity Criteria (NCI-CTC). Occurrence of any adverse event and occurrence of any serious adverse event (anytime during the study) was presented. These events were also be described by nature (Primary System Organ class and Preferred Term), severity and causal relationship to drug administration.

Correlation analyses between selected molecular parameters and clinical data to identify molecular biomarkers like PD-1, PD-L1 and PD-L2) and immune cell infiltrates (like e.g. IGHM, CD3, CD8, FOXP3, CD68, CD205) as well as chemokines (CXCL9. CXCL10, CXCL13) and invasion markers (MMP7, MMP9) in tumor tissue and blood samples predictive for ORR, TTR, recurrence free survival and OS. Analyses will be performed by immunohistochemical and molecular methods in a central lab.