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.
Protocol
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. “
By Gareth MacDonald
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