The use of immunotherapy for pancreatic cancer has had limited exposure, but Aduro BioTech, Inc, has had phase II success with an approach in which two vaccines are administered. The vaccines, GVAX Pancreas and CRS-207, are administered to patients sequentially.
“It has been shown previously in the vaccine field that when combining two vaccine modalities that immune responses are superior to a single vaccine modality,” said Dirk Brockstedt, PhD, senior vice president of Research and Development at Aduro Biotech, in an interview with Oncology & Biotech News
This knowledge, along with positive analyses from preclinical and phase I research, led to Aduro’s phase II investigation of the vaccine combination.
Results from the phase II study demonstrated that treatment with GVAX Pancreas and CRS-207 improved overall survival (OS) and doubled the 1-year survival probability for patients with previously treated, metastatic pancreatic ductal adenocarcinoma. The findings were presented by lead author Dung T. Le, MD, an assistant professor of Oncology of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, during an oral presentation at the 2014 Gastrointestinal Cancers Symposium in San Francisco.
In the study, patients were randomized to receive either the combination of GVAX Pancreas and CRS-207 (Arm A), or the GVAX Pancreas vaccine only (Arm B). Researchers reported that patients in Arm A demonstrated a median OS of 6.1 months compared with 3.9 months in Arm B (HR = 0.54; P
= .011). One-year survival probability for patients in Arm A was 24% as compared to 12% in patients in Arm B. According to the Aduro, the study was stopped early because it had met the primary efficacy endpoint at a preplanned interim analysis.
A phase IIb trial was initiated shortly after data from the phase II study were presented.
The company reported that the phase IIb study, ECLIPSE trial (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting), will enroll approximately 240 adults with previously-treated metastatic pancreatic cancer, involving more than 20 clinical trial sites in the United States and Canada. Safety, immune response, and efficacy will be evaluated.
In this three-arm trial patients will be randomized to receive GVAX Pancreas, low-dose cyclophosphamide, and CRS-207; CRS-207 only; or chemotherapy. The primary endpoint is OS.
“The goal of the study is to confirm results from the previous study and to compare overall survival to currently used therapy,” said Brockstedt. “We’re interested in assessing whether the combination therapy is truly required. From the previous phase II study, it’s clear that if you compared the combination therapy to just GVAX alone, the combination treatment is superior and led to an increase in overall survival,” Brockstedt said.
Eventually, the company would like to determine if GVAX is actually contributing to this improved survival rate. Brockstedt said that “from a business perspective, developing a single biologic is a simpler development path than developing two biologics.” He noted that there are regulatory challenges, as well. “In a combination treatment, the manufacturer has to demonstrate the contribution of each modality to safety and efficacy. So we’re addressing this in the phase IIb study now, so that we have a relatively straightforward phase III study moving forward.”
According to Aduro, the GVAX family of vaccines is derived from human cancer lines that are genetically modified to secrete GM-CSF, an immune-stimulatory cytokine.
CRS-207 is based on attenuated Listeria monocytogenes strains that have been genetically modified to induce potent innate and T cell-mediated immunity, specific for tumorassociated antigens. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is overexpressed in many cancers, including non-small cell lung, ovarian, and gastric, as well as mesothelioma.
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