California based Aduro announced the partial clinical hold last night. It explained that a blood sample from a pancreatic cancer patient who presented with gastrointestinal symptoms had tested positive for Listeria suspected to be derived from the candidate cancer vaccine, CRS-207.
CRS-207, like Aduro’s therapeutic candidates, consists of a genetically modified version of the bacteria Listeria monocytogenes that has had genes required for replication replaced with those encoding protein antigens.
The idea is that while they can no longer replicate, the modified bugs can prompt the immune system to initiate a response to the specific target antigen.
Aduro said it is revising all of its study protocols in light of the clinical hold, including those related to the administration of antibiotics following treatment with any of its LADD-based candidates.
The incident is not the first time concerns have been raised about the technology.
In a US Securities and Exchange Commission (SEC) filing last September, Aduro disclosed that one subject treated with CRS-207 in an earlier trial had been treated with low-dose cyclophosphamide after being diagnosed with listeriosis.
At the time it said: “Several weeks after the CRS-207 infusion, the patient developed symptoms suggestive of an infection; therefore, per institutional practice, urine, stool and blood samples were collected.
“The blood culture from the port site was positive for Listeria monocytogenes, and was determined subsequently to be CRS-207 while all other cultures, including from the peripheral vein, were negative.”
Aduro is not the only firm to have an attenuated-listeria-based therapy trial put on hold.
In October 2015 the FDA told Advaxis to halt trials of its product candidates: axalimogene filolisbac; ADXS-PSA and; ADXS-HER2 – which all use attenuated Listeria to elicit an immune response – after one subject tested positive for the bacteria.
The hold was lifted last December.