CRS-207 consists of modified versions of the bacteria Listeria monocytogenes that have had genes required for replication replaced with genes encoding mesothelin, a protein which is overexpressed by cancerous cells.
In contrast, Keytruda (pembrolizumab) is a monoclonal antibody that targets PD-1, a protein receptor that allows some cancers to escape detection by the immune system.
Aduro spokeswoman Susan Lehner told us “preclinical data that suggests an anti-cancer synergy [is] achieved with the two compounds, with CRS-207 being used to induce an immune response and a PD-1 checkpoint inhibitor to supress the cancer’s ability to evade the immune system.”
She went on to say: “We expect to launch the Phase II trial evaluating CRS-207 in combination with Keytruda for the treatment of patients with MPM in the first half of 2017” adding that the study will be conducted in the US.
The trial is the second Aduro and Merck have announced this year. In January, they said they plan to test a regimen combining Keytruda and CRS-207 for the treatment of gastric cancer.
News of the study comes seven months after the US Food and Drug Administration (FDA) lifted a partial hold on it had imposed on trials of CRS-207 and all candidates based on Aduro’s LADD (live, attenuated, double-deleted Listeria mononcytogenes) platform.
A month earlier the US regulator told Aduro to halt enrolment in trials of LADD-based drugs after Listeria was found in a sample taken from the in-port of a medical implant worn by a participant in a Ph IIb trial of CRS-207.
While the patient showed no signs of systemic infection, the positive test raised concerns the modified bacteria can form biofilms on medical implants. A similar incident occurred in a separate trial conducted by Aduro in 2015.
To address this, Aduro changed trial protocols for its LADD therapies to extended patient surveillance, excluded subjects with certain prosthetic implants and added guidance on the administration of prophylactic antibiotics.
The plan for the new study reflects these changes according to Lehner, who said: “The clinical protocol relating to the Phase 2 clinical trial of CRS-207/Keytruda incorporates the slight protocol modifications that were implemented in response to the partial clinical hold that was briefly in place in late 2016. “