Combination treatment with the GVAX pancreatic cancer vaccine and CRS-207 vaccine extended survival with manageable toxicity compared with the GVAX pancreatic cancer vaccine alone in patients with metastatic pancreatic ductal adenocarcinoma, according to results of a randomized phase 2 study presented at the 2014 Gastrointestinal Cancers Symposium.
“This is the first time a randomized study has shown that immunotherapy is effective in pancreatic cancer,” Dung T. Le, MD, assistant professor of medicine at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, said in a press release. “Various chemotherapy drugs are used, but there are no standard treatment options for second- or third-line therapy in this setting. We’re excited these patients may soon have an alternative to chemotherapy that could come with fewer side effects.”
Le and colleagues evaluated data from 90 patients with an ECOG performance status of 0 to 1. Fifty-one percent of patients had received two or more prior chemotherapy regimens.
Sixty-one patients randomly assigned to the combination arm received two doses of low-dose cyclophosphamide plus GVAX Pancreas (BioSante Pharmaceuticals) — which consists of irradiated, granulocyte-macrophage colony–stimulating factor-secreting allogeneic pancreatic cell lines — followed by four doses of CRS-207 (Aduro BioTech), a live-attenuated Listeria monocytogenesthat expressesmesothelin.
The remaining 29 patients received six doses of low-dose cyclophosphamide plus GVAX alone every 3 weeks.
Median follow-up was 7.8 months.
Median OS was 6.1 months in the combination arm and 3.9 months in the GVAX-only arm (P=.011).
Among patients who received three or more doses, median OS was 9.7 months for those in the combination arm vs. 4.6 months for those assigned to GVAX alone (P=.0074).
Researchers noted a significant difference in median OS between the two study arms when comparing patients who had undergone two or more prior treatment regimens (5.1 months for the combination arm vs. 3.7 months for the GVAX-only arm; P=.001).
CA19-9 stabilization occurred in 32% of patients in the combination arm compared with 13% of patients in the GVAX-only arm (P=.06).
The most common toxicities observed in the CRS-207 arm were transient fevers, rigors and lymphopenia. The most common toxicity related to the GVAX vaccine was local reaction.
“The immunotherapy combination of cyclophosphamide and GVAX plus CRS-207 doubled the 1-year survival probability,” Le said during a press conference. “Subjects who received at least three doses of the combination had a doubling of the median OS in this very-difficult-to-treat cancer, in a previously treated patient population. An additional clinical study of the combination treatment is underway in a three-arm study testing the combination, CRS-207 alone and chemotherapy alone.”
For more information:
Le DT. Abstract #177. Presented at: 2014 Gastrointestinal Cancers Symposium; Jan. 16-18, 2014; San Francisco.
Disclosure: The researchers report employment or leadership positions with, stock ownership in, and royalties from patents licensed to Aduro Biotech.