Merkel cell carcinoma (MCC) is a rare, aggressive type of skin cancer. It is less common than melanoma, but patients are three times more likely to die from it. 

In 2017, Avelumab (brand name Bavencio) became the first FDA approved systemic therapy and the first treatment of any kind approved for metastatic MCC. This was also the first approval from the FDA of this drug, for any disease. 

Bavencio targets the PD-1/PD-L1 pathway (proteins found on the body’s immune cells and some cancer cells). By blocking these interactions, Bavencio may help the body’s immune system attack cancer cells. In December 2018, pembrolizumab was approved for MCC, based on a trial led by a Seattle-based team. 

A lymphocyte destroying a cancer cell. Courtesy: Cancer Immunotherapy Trials Network
A lymphocyte destroying a cancer cell. Courtesy: Cancer Immunotherapy Trials Network

Now researchers have received $12.4 million to study why patients do or do not respond to PD-1 blockade therapy, determine relevant immune evasion mechanisms, and identify therapies likely to be beneficial for this and other immunogenic cancers.

In particular, two paradigm-shifting issues will be explored: the importance and utility (via a clinical trial) of antigen-specific T cell receptor (TCR) avidity in controlling cancer, and identification of tumor-intrinsic and innate immune-evasion mechanisms that can be targeted to broaden the adaptive immune response in PD-1 pathway blockade refractory patients.

Funding comes from a Program Project Grant from the National Cancer Institute for $12.4 million over five years. 

Dr. Paul Nghiem, professor and head (Dermatology) was a senior investigator on the avelumab and pembrolizumab trials, and a Seattle-based team he led conducted the foundational work on the role of immune cells in MCC that paved the way for immunotherapy trials in the disease.

Nghiem is the Principal Investigator of this P01 and project leaders from the Department of Medicine include Drs. David Koelle and Phil Greenberg and co-investigators Aude Chapuis and Shailender Bhatia.

“Our UW/Fred Hutch team is incredibly grateful to have secured funding for this project that brings powerful immune/oncology expertise to bear on Merkel cell carcinoma," said Nghiem. "It is a disease that has already taught us a lot about more common cancers and how we can use the immune system to target them.”

The research will be supported by the National Cancer Institute of the National Institutes of Health under Award Number P01CA225517.