NCT05185739

Perioperative Pembrolizumab and Lenvatinib in Resectable Hepatocellular Carcinoma (HCC)

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pre-operative Pembrolizumab (200mg IV every 3 weeks) for 2 cycles
DRUG	Lenvatinib	Pre-operative Lenvatinib (8 or 12mg PO once daily according to bodyweight \<60gk≥) for 6 weeks
DRUG	Pembrolizumab and Lenvatinib	Pre-operative combination of pembrolizumab and lenvatinib at the standard doses and duration as per cohort 1 and 2

Timeline

• Start date: 2022-08-25
• Primary completion: 2028-07-01
• Completion: 2030-07-01
• First posted: 2022-01-11
• Last updated: 2024-12-06

Locations

11 sites across 1 country: United Kingdom