Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Pembrolizumab

Lenvatinib

Liver Extracts

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Pre-operative Pembrolizumab (200mg IV every 3 weeks) for 2 cycles

Pre-operative Lenvatinib (8 or 12mg PO once daily according to bodyweight \<60gk≥) for 6 weeks

Pre-operative combination of pembrolizumab and lenvatinib at the standard doses and duration as per cohort 1 and 2

Pembrolizumab and Lenvatinib

Michelle Hung

Marain Duggan

Tim Meyer, BSc MBBS PhD FRCP

This is a multicentre randomised 3-arm phase II clinical trial in patients with resectable Hepatocellular Carcinoma (HCC). Sixty patients will be randomized 1:1:1 to 6 weeks of pre-operative therapy with: pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib followed by up to 12 months treatment with post-operative pembrolizumab. The aim of the study is to compare the efficacy of pembrolizumab combined with lenvatinib with that of pembrolizumab and lenvatinib alone in terms of major pathological response in patients with resectable HCC. Major pathological response will be defined by the proportion of patients with less than 10% viable tumour at resection.

Hepatocellular Carcinoma (HCC), or Liver cancer, is the second most common cause of cancer-related death worldwide and is the most rapidly increasing cause of cancer-related death in the West. The only potentially curative options are transplantation, surgical resection and ablation. Both surgical resection and ablation are associated with a high rate of recurrence and 70% of resected patients relapse within 5 years. To date, no standard adjuvant therapies have been approved. Recent studies provide evidence that immunotherapy may address a significant unmet need in the management of HCC.

Furthermore, there is also a rationale for pre-operative therapy which has been shown to be superior to a postoperative treatment approach as supported by pre-clinical studies. The feasibility and outcomes of this approach have recently been reported in the setting of lung cancer. Lenvatinib, an immunotherapy drug, has been approved as a first treatment option in HCC. Pembrolizumab, another immunotherapy treatment has been evaluated as first treatment option in HCC in two clinical trials. The combination of these two drugs has been explored in HCC in early phase trials.

The aim is to compare the efficacy of pembrolizumab (a type of immunotherapy designed to 're-awaken' the immune system) combined with lenvatinib (an anti-cancer drug that is a multiple kinase inhibitor) with that of pembrolizumab and lenvatinib alone in patients with resectable Hepatocellular Carcinoma.

Treatment lasts for up to 18 months. Depending on when patients are recruited, patients will be followed up for a minimum of 1 year and maximum of 3 years, following the end of their post-surgery treatment. It is expected that it will take 24 months to recruit all the patients.

This is a randomised 3-arm phase II clinical trial in patients with resectable HCC. Sixty patients will be randomized 1:1:1 to pembrolizumab, lenvatinib or the combination of pembrolizumab and lenvatinib.

Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

PRIMER-1 Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

The primary aim of the study is to test the hypothesis that the combination of pembrolizumab and lenvatinib result in a higher rate of major pathological response than either drug used as a single-agent in patients with resectable hepatocellular carcinoma.

The hypothesis is that the radiological response rate of pembrolizumab and lenvatinib in combination is greater than that of pembrolizumab and lenvatinib as single agents. Measured by RECIST 1.1 and mRECIST performed pre-operatively and compared with pre-treatment baseline imaging)

Relapse free survival at 12 months from surgery

Defined as the proportion of patients with surgery delayed by more than 4 weeks from the planned surgery date due to IMP-related adverse events (AEs) or serious adverse events (SAEs))

based on the Clavien-Dindo classification

measured by the proprtion of patients mpleting protocol defined study-drug intervention.

Incidence and of adverse events (AEs) reported. Events will be classified according to CTCAE V5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London
Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)	NCT05185739	Hepatocellular ...	Pembrolizumab Lenvatinib Pembrolizumab a...	18 Years -	University College, London

Spots Global Cancer Trial Database for liver cancer,