Phase III Study of MK-3475 + Best Supportive Care in Subjects with HCC

• Research type

  Research Study

• Full title

  A Phase III Study of Pembrolizumab (MK-3475) vs. Best Supportive Care as Second-Line Therapy in Subjects with Previously Systemically Treated Advanced Hepatocellular Carcinoma (KEYNOTE-240)

• IRAS ID

  200096

• Contact name

  Debashis Sarker

• Contact email

  debashis.sarker@kcl.ac.uk

• Sponsor organisation

  Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Eudract number

  2015-004567-36

• Clinicaltrials.gov Identifier

  NCT02702401

• Duration of Study in the UK

  2 years, 4 months, 9 days

• Research summary

  Summary of Research
  Liver cancer is the second world leading cause of cancer deaths. Most Hepatocellular Carcinoma (HCC) arises in the setting of liver cirrhosis from varied causes, including viral hepatitis or excessive alcohol consumption, making it a heterogeneous malignancy (tumour that can spread, cause serious and fatal damage).
  Despite advances in early detection, liver transplantation and liver-directed therapies, about 70% of HCC patients present with advanced disease with no curative option. HCC is resistant to most traditional chemotherapy agents, and the median survival for patients with advanced disease is 6–9 months without therapy. There are no agents or combinations approved for previously treated HCC (or second-line HCC), underscoring its high unmet medical need.
  Programmed cell death 1 (PD1) is a protein present on the surface of immune cells which fight cancer. When immune cells encounter cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) which are proteins on the surface of cancer cells. The activated immune cells become exhausted or die thus stopping them from attacking the cancer. The study drug pembrolizumab is a potent and highly selective humanised monoclonal antibody developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
  The purpose of this phase III study which will last approximately 36 months, is to evaluate the safety and efficacy of pembrolizumab plus Best Supportive Care (BSC) as compared to placebo plus BSC evaluating Progression Free Survival (PFS) and Overall Survival (OS).
  Approximately 408 male/females subjects older than 18 with previously systemically treated HCC will be randomised at a 2:1 ratio to receive pembrolizumab 200 mg intravenous (IV) plus BSC every 3 weeks or placebo IV plus BSC every 3 weeks.
  The study is funded by Merck Sharp & Dohme Limited and will take place at 3 study centres in the UK.

  Summary of Results
  https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agba4yu73OCS9U-2BkKS40W1kfZLMhYNSL6uAQ3D-2BHysQkrDtDBNt-2FRqn7ir5t4LQcHnn8M7dk5REFhjYfCMyk0N9T-2FjWckmyLc1TTMlFi0hzxJqdFljkWGO84JO9D1almvvQw-3D-3Dml7G_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIG0DSiYRKS98Cqys4wWuB-2F6d-2BKFguMnnwPn5-2F3-2BPoEFPxKexOVehF7yuztXSfgddFD0qaRBx-2Fyx7HnwjHchrzla6lQqHeMdzjotphUcZNf2r2iwzbHqjCPl-2Bl5DGTmT8KdAAFfpuBrnSuWCvxmQGezuRyLn13GnfWOPV0M2suG7Q-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cb2d2db8ba7c249147da308da9735c68a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988554477622771%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=eoLbq7KCcJqzGpQcDVWY8azmnCx1mIvSm8%2F5FQQ4zhY%3D&reserved=0

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  16/LO/1514

• Date of REC Opinion

  23 Sep 2016

• REC opinion

  Favourable Opinion