A Phase II Trial of MK-3475 in Subjects with Bladder Cancer

• Research type

  Research Study

• Full title

  A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects with Advanced/Unresectable or Metastatic Urothelial Cancer

• IRAS ID

  170073

• Contact name

  Bin Zhao

• Contact email

  Bin.Zhao2@merck.com

• Sponsor organisation

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

• Eudract number

  2014-002206-20

• Duration of Study in the UK

  3 years, 0 months, 1 days

• Research summary

  Summary of Research
  Urothelial cancer describes a range of tumours occurring in the bladder, renal pelvis, ureter, and urethra. The incidence of bladder cancer exceeds 300,000 cases annually, ranking it as the seventh most common cancer worldwide. Urothelial carcinoma is the predominant type of bladder cancer in the United States and Western Europe, accounting for approximately 90 percent of bladder cancers.

  Cisplatin-based combination chemotherapy is standard first-line treatment for patients with advanced bladder cancer. The median survival with these regimens is 13 to 15 months, and 5% to 15% of patients attain long –term survival. However, cisplatin ineligibility is common because of renal dysfunction. Furthermore, hearing loss, Grade 2 neuropathy, and heart failure function may also confer cisplatin ineligibility. Thus, there remains a significant medical need for well tolerated active therapies in this population.

  This study monitors the anti-tumour activities of MK3475, pembrolizumab, a potent and highly selective humanised monoclonal antibody designed to block the interaction between PD-1 (immune cell protein which fights cancer) and its ligands PD-L1 and PD-L2. Blocking PD-L1 activity increases immune attack on cancers.

  This study will recruit patients with advanced/unresectable (inoperable) or metastatic urothelial cancer who have not yet received chemotherapy and are ineligible for cisplatin treatment. It will be administered as 1st line therapy.

  This is an un-blinded, open-label study and aims to investigate the association between PD-L1 protein expression in tumour tissues and the anti-tumour activity of MK3475 by immunohistochemistry.

  Patients will receive 200mg of MK3475 every three weeks and be monitored regularly for safety and clinical and/or radiographic evidence of disease progression. The trial will require approximately 36 months from patients consent until last visit.

  About 350 patients will be enrolled worldwide.

  The study will take place at 5 UK Hospitals.

  The study is funded by Merck Sharp & Dhome Ltd.

  Summary of Results
  : https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5Bdj8o1FpylFwbn362DUDJ-2Fz4T3lVWjUgkXasupCn5aPVWWs-2FmIxHjwy1HfDOmocGvHxKwkrEI9tUpQ9QPjvb8gqJXxt_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJaYZHzhfPPTv8Ehtd6675CrfP3TozNjgvAYPTqgal0ITZhnKqXI3DjWvl6TmFufbpgGv-2FWX-2FFSsoNubQKHqUgN5eeYSuoTolViGQUhVv4zaHAVOcY50PMDKG9Al0uvwIRrpTIQHv2-2BtafGeufVobjvT2Udp9hF8daY7cxBaNB8tA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cbca14094aaef442abfed08db29642345%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638149282280033264%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3mF0ymT4k5M6NwQOGaNodfJuFvGfk9h89SLdtGzxvRY%3D&reserved=0

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  15/LO/0236

• Date of REC Opinion

  7 Apr 2015

• REC opinion

  Further Information Favourable Opinion