Merck & Co’s onco-immunotherapy Keytruda has picked up its third breakthrough therapy designation in the US, this time after showing promise as a treatment for microsatellite instability high (MSI-H) metastatic colorectal cancer.

The move comes on the back of early clinical evidence suggesting that the PD-1 inhibitor could offer a substantial improvement over existing therapies, and should help speed up its development and review pathway for this indication.

Merck is currently conducting a Phase II registration study (KEYNOTE-164) to assess the efficacy and safety of Keytruda (pembrolizumab) based on microsatellite instability status in patients with previously treated advanced colorectal cancers, and is also planning a Phase III study (KEYNOTE-177) in a treatment naïve patient population.

Testing tumours for microsatellite instability can identify patients with defective DNA mismatch repair systems (MMR), a mechanism by which cells can recognise and repair genetic mismatches generated during DNA replication. 

Around 20% of Stage II, 10% of Stage III and 5% of Stage IV colorectal cancer cases are considered MSI high, and overall MMR-deficiency is present in up to 20% of non-hereditary CRCs and most hereditary CRCs associated with Lynch Syndrome.

Keytruda was previously awarded breakthrough status in the US for advanced melanoma and non-small cell lung cancer, and was subsequently awarded accelerated approval for both conditions.