US-based pharmaceutical company Merck has reported positive results from the Phase II trial of its anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with advanced cancers characterised as deficient for DNA mismatch repair (MMR).
The Phase II trial evaluated the clinical activity of KEYTRUDA monotherapy administered in proportions 10mg/kg every two weeks, in patients with previously treated, progressive metastatic disease with or without MMR deficiency. It demonstrated a consistent safety of the drug.
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The trial’s key endpoints was overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) measured by RECIST v1.1, and overall survival (OS).
Results from the trial showed that among previously treated patients with MMR-deficient tumours, there was an ORR of 53% in patients with a range of advanced, non-colorectal solid tumours and an ORR of 57% in patients with advanced colorectal cancer.
In contrast, no responses were observed in patients with advanced colorectal cancer whose tumours were characterised as MMR-proficient.
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Merck research laboratories oncology late-stage development therapeutic area head and senior vice-president Dr Roger Dansey said: "We continue to be encouraged by the findings of this ongoing study evaluating Keytruda in patients with mismatch repair deficient tumours.
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By GlobalData"Characterisation of biomarkers with the potential to predict clinical outcomes for patients receiving immune therapy for cancer is an important element of our clinical programme for Keytruda."
Three groups were evaluated in the trial, including MMR-deficient non-colorectal cancers, MMR-deficient colorectal cancer and MMR-proficient colorectal cancer.
In order to detect microsatellite instability, MMR status was evaluated locally using a standard immunohistochemistry (IHC) or polymerase chain reaction (PCR)-based method.
An analysis of tumour DNA for microsatellite instability identifies tumours with defective DNA MMR systems.
In normal cells, DNA MMR allows the recognition and repair of genetic mismatches caused during DNA replication.
A defective MMR system causes a chronic DNA mismatch that extends into the genetic code as mutations.
Tumours with DNA MMR-deficiency exist in thousands, especially in regions of repetitive DNA known as microsatellites.
Tumours found to have mutations in select microsatellite sequences, known as microsatellite instability (MSI), are considered DNA MMR-deficient.
Humanised monoclonal antibody Keytruda boosts the body’s immunity system to detect and fight tumour cells. It resists PD-1 from interacting with its ligands, PD-L1 and PD-L2, subsequently activating T-lymphocytes which may affect both tumour and healthy cells.
