Aduro exits clinical hold after trial tweaks quell Listeria fears

FDA building
The FDA and Aduro have agreed on changes to CRS-207 trial protocols.

The FDA has lifted the partial clinical hold it placed on trials of Aduro Biotech’s CRS-207 cancer vaccine last month. The resolution clears Aduro to resume enrollment in an ongoing phase 1/2 trial and push ahead with preparations for a study to test CRS-207 in combination with an anti-PD-1 compound.

CRS-207 is made by reengineering Lis­te­ria mono­cy­to­genes to neuter the bacteria and make it express the mesothe­lin protein. This process is intended to ensure that the bacteria cannot cause Listeria, but does trigger a cancer-fighting immune response. The snag, for Aduro, is that two cases of Listeria did occur in the 350 patients treated prior to the initiation of the partial clinical hold. Those cases were linked to in-dwelling medical device ports, spaces where bacterial biofilms can form.

Berkeley, CA-based Aduro got out from under the clinical hold by tweaking its trial protocol to cut the risk of similar cases occurring in the future and ensure it reacts quickly in the event they do. To head off the biofilm threat, Aduro is excluding patients with certain hard-to-remove prosthetic devices from CRS-207 trials.

Knowledge of the potential for CRS-207 to cause problems for people with prosthetics goes back years. Anza Therapeutics tested CRS-207 in humans before offloading the asset to Aduro in 2009. The exclusion criteria for an Anza trial protocol filed late in 2007 bar patents with “artificial (prosthetic) joint or other artificial implant or devices that cannot be easily removed” from participating in the study.

Aduro has gradually tweaked the wording of the line since starting its own clinical trials of CRS-207 in 2011. The first protocol included a near word-for-word copy of Anza’s line about prosthetics, adding only that “there are some exceptions.” A subsequent trial protocol listed “dental and breast implants and biliary stents and mediports” as the exceptions. In 2013, Aduro tweaked the exclusion criteria to allow patients with prosthetic heart valves and other previously prohibited implants into its studies, provided the device was placed at least one year prior and hadn’t previously caused infections.

The new wording of the exclusion criteria has yet to go live on, but Aduro’s statement suggests it will place greater restrictions on the ability of people with prosthetic implants to join its studies.

Aduro has also agreed with the FDA to extend patient surveillance and give antibiotics to recipients of CRS-207 who may take immunosuppressive drugs.

These changes prompted the FDA to give Aduro the green light to resume enrolling patients in trials of CRS-207. Aduro plans to start a phase 2 trial of CRS-207 in combination with an anti-PD-1 drug in mesothelioma patients in the first half of next year.