Blog January 16, 2017

FDA Grants Priority Review for KEYTRUDA® IN MSI-H Cancers

On November 28, the U.S. Food and Drug Administration granted Priority Review to Merck’s Supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab) in the new indication of microsatellite instability-high (MSI-H) cancer. MSI-H is a biomarker caused by a deficiency in a cell’s ability to repair errors in DNA sequences that occur during cell division. The FDA is expected to announce its decision on KEYTRUDA’s approval in this new indication by March 8, 2017. The FDA recently granted Breakthrough Therapy Designation to KEYTRUDA for unresectable or metastatic MSI-H non-colorectal cancer, and previously granted it for the treatment of patients with unresectable or metastatic MSI-H colorectal cancer.


We believe this is a noteworthy development, as it could potentially lead to the first approval for an immuno-oncology product in a somewhat tumor-agnostic indication, using a specific biomarker to identify those patients most likely to benefit. While other companies have also been looking at MSI-H as a useful biomarker for patient selection, most trials we are aware of are focused on cancers affecting a specific organ type, with a focus on colorectal and endometrial cancers. In contrast, the data in support of Merck’s filing included multiple patient cohorts from five uncontrolled, open-label Phase I/II trials across MSI-H indications.


The FDA’s action raises several questions of interest, where we will eagerly be watching to learn the answers:

  • What will the ultimate label look like? Will there be a separate label for each tumor type or a broad MSI-H label?
  • Will the drug administration/dosing be the same across tumor types?
  • Is this the starting point for further tumor-agnostic approvals?
  • Will a move towards tumor-agonistic, biomarker-driven approvals increase the role of the molecular pathologist? How will it affect other specialties in oncology?
  • How will a broad, tumor-agnostic biomarker-driven approval affect other drug developers who are currently only going after a single tumor type? Will they all need to adapt to a change in overall strategy?


The potential approval of Keytruda in MSI-H has expanded the focus beyond PD-L1 for immuno-oncology, providing another tool for patient selection.  As we discussed in our recent article “How Immuno-Oncology Is Turning Biomarker Development On Its Head,” biomarker identification and development faces unique challenges in immuno-oncology, given the highly competitive and fast moving environment.  In this case, MSI status has provided drug developers with the opportunity to enter in indications where response rates were generally low in an unselected patient population, and with new information on why some patients respond better than others to IO agents.  A new biomarker and a tumor agnostic approach to patient selection may well provide the competitive differentiation for which IO drug makers have been searching.