Novel immunotherapy agent CRS-207 recently won orphan drug status from the U.S. Food and Drug Administration (FDA), which makes it more likely you’ll someday soon see it marketed specifically for the treatment of mesothelioma.
The significance of orphan drug status is that it paves the way for the makers of therapeutic products such as CRS-207 to enjoy seven years of marketing exclusivity in the U.S., as well as receive funding for clinical trials plus various tax breaks.
These advantages incentivize manufacturers to keep pushing forward with development of their new and promising products, thereby benefitting patients.
But there’s a catch. Drug makers must first convince the FDA to approve the product for nationwide distribution and use.
That’s what the maker of CRS-207 is trying to do – obtain full FDA approval. Officials of the manufacturer, Aduro Biotech Inc., express confidence they will succeed.
The key to it all is providing to the FDA evidence that CRS-207 is safe and effective. The company says that part of that proof will come from the published results of a Phase 1b clinical trial it is now conducting through December of this year.
Agent Targets Mesothelioma Cells
CRS-207 is an engineered molecular-targeting system based on Aduro Biotech’s proprietary live-attenuated, double-deleted Listeria monocytogenes immunotherapy platform.
CRS-207 has an affinity for mesothelin, which mesothelioma cells overexpress. When CRS-207 docks into one of a mesothelioma cell’s mesothelin receptors, it triggers an innate and T cell-mediated adaptive immune response that disrupts the mesothelioma cell’s biological processes.
The genetic modification of the Listeria monocytogenes employed in CRS-207 is performed in order to reduce their capacity to cause disease, while maintaining their ability to stimulate potent immune responses.
The Phase 1 clinical trial of CRS-207 began in 2012 and last year the company disclosed some interim findings with regard to the therapeutic agent’s performance.
According to Aduro Biotech, CRS-207 induced at least a partial response in three-quarters of the 16 participating mesothelioma patients. Even more promising, mesothelioma was stabilized in a handful of them.
On average, mesothelioma patients testing CRS-207 experienced 7.5 months of progression-free survival. For one mesothelioma patient, progression-free survival extended beyond 19 months.
Aduro Biotech calls the results seen up to this point encouraging – so much so that it has expanded the clinical trial to take in a total of up to 40 more mesothelioma patients. Enrollment is now underway.
Mesothelioma Patient Regimen Described
Mesothelioma patients who participate in the clinical trial receive two vaccinations of CRS-207 at two-week intervals.
Then, after another two weeks, they begin receiving the first of up to six cycles of chemotherapy in the form of pemetrexed and cisplatin. These are administered at intervals of three weeks.
Three weeks after chemotherapy ends, the mesothelioma patients are given a booster CRS-207 dose. This is followed by a second booster dose three weeks later – and possibly additional boosters as warranted over time.
Aduro Biotech’s researchers monitor the responses of the mesothelioma patients during follow-up visits staggered eight weeks apart.
At the follow-up visits, mesothelioma patients can expect to receive CT scans, sometimes supplemented by PET-CT and MRI studies. Tumor biopsies may also be taken at various stages of the clinical trial.
The clinical trial is being held at mesothelioma treatment centers in California, Florida, Illinois, Maryland and Pennsylvania.
To enroll, prospective participants are required to have mesothelioma of either the epithelial or biphasic cell type. You can’t participate if you have the sarcomatoid type of mesothelioma.
Also, participants must have mesothelioma advanced enough that it likely cannot be treated with surgery. At the same time, it can’t be so far advanced that expected survival is less than six months.
The doors are closed as well to mesothelioma patients who had any prior radiation or biologic therapy or systemic chemotherapy.
If you’d like to find out more about this clinical trial, contact Yvonne Malory, RN, by phone at 301-402-0255 or by email at malloryy@mail.nih.gov and refer to the clinical trial by its numeric identifier, NCT01675765.
