How CMP-001 works
The immune system identifies and attacks abnormal cells, including cancer. Sometimes the response is not strong enough to slow a tumor’s growth. And some tumor cells develop ways to evade immune cell detection. That’s where Immunotherapy drugs such as CMP-001 come in — by acting to boost the immune response against cancer.
CMP-001 is a short piece of DNA, called an oligonucleotide, that Checkmate designed to mimic the DNA of bacteria. It encapsulated the DNA in noninfectious virus-like particles, or VLPs.
The company created CMP-001 to be administered directly to a tumor. When this occurs, the immune system sees VLPs as foreign. It generates immune cells called antigen presenting cells that release the DNA from the VLPs.
Inside the antigen presenting cells, the DNA activates a protein called toll-like receptor-9 (TLR9), which views the DNA as a harmful bacteria. TLR9 then triggers a signaling pathway that boosts immune system response. The pathway does this by activating immune cells that surround it and by recruiting immune T-cells capable of killing tumor cells.
Checkmate designed CMP-001 to be injected directly into a tumor so the revved-up immune response would occur at the tumor site itself, increasing its punch.
The company is looking at using CMP-001 as a stand-alone therapy and in combination with immunotherapies known as immune checkpoint inhibitors. The inhibitors remove the mechanisms that some cancer cells use to evade immune system detection but do not boost the immune response themselves. The idea behind combining them with CMP-001 is to both enhance the immune system’s ability to recognize cancer while increasing the strength of the response.
Preclinical-trial studies showed that CMD-001 as a stand-alone therapy reduced tumor growth and increased the survival of mice with lymphoma. Adding an immune checkpoint inhibitor that targeted the PD-1 protein to CMD-001 generated an even better response. PD-1 is found on the surface of a number of cancers. Checkmate presented the study’s findings at the 58th American Society of Hematology annual meeting in 2016.
CMP-001 in clinical trials
The trial will occur in two parts. In the first part, researchers will increase doses of CMP-001 and Keytruda to find an optimal treatment for a Phase 2 trial.
The second part of the study will assess CMP-001’s safety, preliminary cancer-fighting ability and pharmacodynamics, or effect on the body. This part will cover CMP-001 as a stand-alone therapy, not with Keytruda. Checkmate presented the design and rationale of the trial at the 2016 American Society for Clinical Oncology annual meeting.
Checkmate is recruiting 76 melanoma patients for a second Phase 1/2 trial (NCT03084640) at three U.S. sites. Some will receive CMP-001 as an injection under the skin and some inside their tumor.
This trial will also be in two parts. The first will assess a combination of CMP-001 and Keytruda, and the second CMP-001 as a stand-alone therapy. The trial is expected to be completed in December 2019.
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