UPDATE: Aduro Biotech announced on December 12 that they have decided to discontinue its CRS-207 clinical trial and wind down each of its trials in mesothelioma. This decision was made based on preliminary results from the trials, as well as a business and commercial assessment.
On November 8, 2017, the Meso Foundation hosted a Meet the Mesothelioma Experts teleconference with Aduro Biotech (Aduro). Moderator Mary Hesdorffer was joined by Natalie Sacks, MD, the chief medical officer at Aduro, and Evan Alley, MD, PhD, the chief of the Division of Hematology and Oncology at Penn Medicine.
Drs. Sacks and Alley provided listeners with information and insight into Aduro Biotech’s mesothelioma clinical trial, which seeks to evaluate the effectiveness of their CRS-207 vaccine in combination with pembrolizumab (Keytruda) in previously treated patients with pleural mesothelioma. Both drugs have singularly demonstrated activity in mesothelioma and preclinical data suggests a synergy in using a combined approach
As explained by Dr. Sacks, CRS-207 is a weakened form of the Listeria bacteria that has been genetically modified to reduce its ability to cause infections, but retain its ability to stimulate the immune system. When used to treat mesothelioma, CRS-207 triggers an immune response against the mesothelin protein that is present on mesothelioma tumor cells.
Dr. Alley filled listeners in on the other drug in the study, Keytruda. Keytruda is a checkpoint inhibitor that blocks a protein called PD-1, which is present on the surface of immune cells called T-cells. Keytruda prevents PD-1 from inhibiting the immune response, which, in turn, allows the T-cells to recognize the cancer cells and attack them.
Aduro Biotech’s new clinical trial is a phase II trial in which previously treated malignant pleural mesothelioma patients will receive both drugs. “The goal of this study is to primarily look to see if combining Keytruda with CRS-207 might show signs of improved activity and synergy,” explained Dr. Alley.
Eligible patients are required to have previously undergone a standard chemotherapy regimen of a platinum drug and pemetrexed, and it is important that they have never had treatment with Keytruda before the trial. Additionally, patients must have the epithelioid or biphasic (predominantly epithelioid) type of pleural mesothelioma, as identified by a pathologist.
Keytruda is well tolerated, as Dr. Alley explained, and adverse effects are seen less than 5% of the time. The side effects that are sometimes seen in patients are primarily autoimmune and involve inflammation. The most common side effect seen is colitis, which can cause diarrhea.
Similarly, Dr. Sacks noted that adverse effects are also rarely seen with CRS-207. Some reactions are a result of the immune system being turned on, including fever and chills, which typically last for only a day.
During the trial, eligible patients go through the first infusion of the drug combination on two separate days to make sure it is well tolerated. Patients are then monitored and undergo blood tests and laboratory tests to both see efficacy and ensure safety. Imaging studies are performed every six weeks to monitor the response to the treatment. If patients are tolerating it and responding, or if the disease is stable, they continue the treatment.
“Mesothelioma is not the most common cancer, but it’s still imperative that we find new and better treatments,” Dr. Sacks said. “Sometimes a clinical trial seems nerve wracking or like a big burden, but you have the opportunity for extra care and for extra attention, and, very importantly, the opportunity to contribute to understanding,” she continued.
“Every breakthrough, every treatment that we have that is a standard was because brave people went forward and enrolled in clinical trials and provided that information to help people in the future to know what is the best therapy to treat this disease,” Dr. Alley added.
For more information on Aduro Biotech’s clinical trial, including eligibility and location information, click here. To listen to the full interview with Dr. Natalie Sacks and Dr. Evan Alley on behalf of Aduro Biotech, visit curemeso.org/experts.
