MK-3475 + MK-7902 Treatment of Locally Advanced or Metastatic UC
Research type
Research Study
Full title
A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma in Cisplatin-ineligible Participants Whose Tumors Express PD-L1, and in Participants Ineligible for Any Platinum-containing Chemotherapy Regardless of PD-L1 Expression (LEAP-011)
IRAS ID
262098
Contact name
Omi Parikh
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2018-003752-21
Duration of Study in the UK
3 years, 7 months, 7 days
Research summary
The global incidence of bladder cancer exceeds 300,000 cases annually with Urothelial Carcinoma (UC) accounting for 90% of bladder cancer in Western Europe and the USA.
UC disproportionally affects the elderly who often have limited treatment options due to coexisting illness. The standard of care for UC patients is cisplatin-containing or platinum-containing chemotherapy. However, only 21% of patients are suitable for treatment with cisplatin and 48% cannot be treated with any platinum-containing chemotherapy.
Early studies have shown that the combination of the study drugs, lenvatinib and pembrolizumab, can help increase the immune response against cancer cells and may provide new treatment options for patients.
Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells meet 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 die thus stopping them from attacking the cancer. The study drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
Lenvatinib works by blocking proteins called Vascular Endothelial Growth Factors which cancer cells can use to help themselves grow. Studies have shown that lenvatinib can also help increase the immune attack on cancers.
This phase III study will last approximately 5 years and will recruit approximately 694 participants aged 18 years or over with advanced/unresectable or metastatic UC who are incompatible with either cisplatin or any platinum-containing chemotherapies. The study will assess the safety and effectiveness of pembrolizumab + lenvatinib versus pembrolizumab + placebo. Participants will be assigned randomly to one of two groups of the study.
The study is sponsored by Merck Sharp & Dohme Limited and will take place at 12 study centres in UK.
REC name
East of England - Essex Research Ethics Committee
REC reference
19/EE/0168
Date of REC Opinion
26 Jun 2019
REC opinion
Further Information Favourable Opinion