A Phase 3 trial of BCG +/- MK-3475 for HR NMIBC (KEYNOTE-676)
Research type
Research Study
Full title
A Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Bacillus Calmette- Guerin (BCG) in Participants with High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) that is Persistent or Recurrent Following BCG Induction (KEYNOTE-676)
IRAS ID
253000
Contact name
Benjamin Ayres
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2018-001967-22
Duration of Study in the UK
5 years, 11 months, 29 days
Research summary
Bladder cancer represents 4.7% of all new cancer diagnoses in the US, with approximately 70% of these classified as non-muscle invasive bladder cancers (NMIBC).
The current standard of care for high-risk NMIBC is surgical removal of the cancer followed by Bacillus Calmette-Guerin (BCG) immunotherapy. While BCG therapy may be successful at preventing early tumour recurrences, 40% of patients progress to muscle invasive disease, of which 20-30% further progress to metastatic disease. There is currently no standard non-surgical treatment for patients with NMIBC after unsuccessful BCG therapy, with the next treatment step being removal of part or all of the bladder, after which patients require lifelong care and monitoring. The development of new treatments that could allow for potential bladder preservation and minimise the risk of recurrent and progressive disease is therefore needed.
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 become exhausted or 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.
This phase III study will last approximately 5 years (3 years treatment; 2 years follow-up) and will recruit approximately 550 participants, aged 18 years or over, with high-risk NMIBC that is persistent or recurrent following adequate BCG induction.
The purpose of the study is to evaluate the effectiveness and safety of pembrolizumab given in combination with BCG, versus BCG therapy only. Participants will be assigned randomly to one of the two arms of the study.
The study is sponsored by Merck Sharp & Dohme Limited. It will take place at four study centres in UK.REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
18/EM/0383
Date of REC Opinion
8 Jan 2019
REC opinion
Further Information Favourable Opinion