Phase 3 study of pembrolizumab/placebo + Enzalutamide + ADT in mHSPC
Research type
Research Study
Full title
A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)
IRAS ID
275931
Contact name
Vincent Khoo
Contact email
Sponsor organisation
Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc.
Eudract number
2019-003633-41
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 3 months, 30 days
Research summary
Prostate cancer represents the second most common cancer diagnosed in men worldwide with an incidence of over 1,000,000 cases and >300,000 deaths annually. While many men diagnosed with locally confined disease may be treated with radiation or surgery, approximately 30% of men have recurring disease and go on to develop metastatic prostate cancer.
Both docetaxel and abiraterone have been shown to prolong overall survival when combined up-front with ADT and are now considered standard of care for men diagnosed with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC). While these therapies are initially effective, the disease often returns, and the effectiveness of other subsequent therapies reduces. Thus, there remains a significant unmet need for novel therapies or combination regimens for patients with metastatic prostate cancer.
Studies have shown that the addition of enzalutamide to ADT resulted in a significant improvement in overall survival.
Pembrolizumab is a type of immunotherapy that stimulates the body's immune system to fight cancer cells. It works by blocking a protein called PD-1 on the surface of T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells. Enzalutamide-resistant tumour cells express significantly increased levels of PD-L1 compared to non-enzalutamide resistant tumour cells. Thus, by blocking the PD-1 receptor, pembrolizumab treatment may increase the immune response to enzalutamide-resistant cells that emerge in response to treatment with enzalutamide.
This clinical trial will study the combination of pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT in the treatment of patients with mHSPC.
Approximately 1232 male participants will be randomly assigned in 1:1 ratio to treatment with pembrolizumab plus enzalutamide plus ADT versus placebo plus enzalutamide plus ADT.
The study is funded by Merck Sharp and Dohme Limited and will take place at eight study centres in UK.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
20/LO/0119
Date of REC Opinion
18 Mar 2020
REC opinion
Further Information Favourable Opinion