KeyImPaCT:Keytruda Immunotherapy Personalized & Combination Treatment
Research type
Research Study
Full title
A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab- (MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)
IRAS ID
238983
Contact name
Martin Forster
Contact email
Sponsor organisation
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eudract number
2017-003134-85
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
E7080-G000-223, EISAI
Duration of Study in the UK
4 years, 5 months, days
Research summary
Non-small cell lung cancer (NSCLC) represents approximately 80-85% of all lung cancers. At the time of diagnosis, approximately 70% of patients have inoperable advanced disease and the 5-year relative survival is 4.3%.
Multiple pembrolizumab based combination therapies show promising treatment. However, it is not clear which patients are most likely to respond to which pembrolizumab-based combinations.
This study will investigate a combination of experimental drugs for the treatment of NSCLC, based on a biomarker-based triage. Study participants within groups defined by a biomarker-based classifier will be randomized to receive pembrolizumab (MK-3475) in combination with MK-4280 or lenvatinib.
The study drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers. 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.
MK-4280 is a monoclonal antibody (proteins that bind to cancer cells and help the immune system fight them) that directly blocks the interaction between lymphocyte-activation-gene-3 (a protein which regulates T-cells) and its ligand. Lenvatinib is another study drug that works by blocking proteins called Vascular Endothelial Growth Factors which cancer cells can use to help themselves grow.
Approximately 192 participants (≥18 years) will be enrolled in group-sequential, adaptive randomization, open label Phase II study which will last approximately 5 years. Each participant will receive pembrolizumab plus MK-4280 or lenvatinib for approximately 2 years, to test safety and effectiveness of these drugs in combination.
The study is funded by Merck Sharp and Dohme Limited and will take place at 3 study centres in UK.
REC name
East of England - Essex Research Ethics Committee
REC reference
18/EE/0352
Date of REC Opinion
16 Jan 2019
REC opinion
Further Information Favourable Opinion