Pembrolizumab+axitinib.vs.sunitinib monotherapy in mRCC
Research type
Research Study
Full title
A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Axitinib versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)
IRAS ID
210861
Contact name
Mei Chen
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2016-000588-17
Duration of Study in the UK
3 years, 8 months, days
Research summary
Renal cell carcinoma (RCC), is a common type of kidney cancer. About 90% of all kidney cancers are renal cell carcinomas. Renal cell carcinoma accounts for 2% - 3% of all adult cancers, representing the 7th most common cancer in men and the 9th most common cancer in women. Worldwide, there are an estimated 209,000 newly diagnosed cases of RCC and an estimated 102,000 deaths per year. Surgery, embolization (blocking of blood-flow to cancer cells), chemotherapy (cancer medicines) or radiation therapy have substantially improved the likely outcome of patients with RCC. However the outcome is very poor in advanced or metastatic (cancer that has spread) cancers.
The medicines used in this study are Axitinib, Sunitinib and Pembroluzimab. Axitinib and Sunitinib are cancer medicines which have shown significant improvement in clinical effect, with acceptable safety profiles in patients with advanced RCC. They work by trying to stop the actions of a protein called vascular endothelial growth factor (VEGF).
Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells come upon 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 test drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
This phase III, active control, open label trial will study the possible activity of pembrolizumab given together with axitinib, and compared to sunitinib. Approximately 840 male and female subjects aged 18 years/above with advanced/metastatic renal cell carcinoma will participate for approximately 2 years. Patients will receive either Pembrolizumab together with axitinib or sunitinib on its own. Patients will have a 50:50 chance of being assigned to either treatment group. Pembrolizumab will not be provided to subjects who progressed on the sunitinib arm.
Enrolled subjects will receive either pembrolizumab as an intravenous solution at 200mg every 3 weeks together with axitinib 5mg twice daily taken by mouth or; 50mg Sunitinib each day for 4 weeks taken by mouth and then off treatment for 2 weeks.Study is funded by Merck Sharp and Dohme Limited and will take place at 4 study centres in the UK.
REC name
London - Dulwich Research Ethics Committee
REC reference
16/LO/1648
Date of REC Opinion
1 Dec 2016
REC opinion
Further Information Favourable Opinion