Aduro Biotech is collaborating with Merck to study the combination of Aduro’s Listeria-based immunotherapy CRS-207 with Merck’s anti-PD-1 Keytruda (pembrolizumab) in gastric cancer patients.
The multicenter Phase 1 clinical trial, which will enroll metastatic gastric cancer patients who failed at least two prior therapies, is expected to begin in the first half of 2017.
CRS-207, Aduro’s most advanced immunotherapy product candidate, belongs to a family of products based on the company’s LADD (live, attenuated double-deleted) platform, which uses Listeria bacteria that are engineered to work as agents that trigger strong immune responses to specific tumor antigens.
CRS-207 elicits immune responses against the mesothelin protein, which is over-expressed in a large variety of tumors, including mesothelioma and non-small cell lung cancer, as well as ovarian, endometrial, pancreatic, and gastric cancers.
“CRS-207 has demonstrated the ability to induce an anti-tumor immune response in clinical trials in other tumor types that over express the tumor antigen mesothelin,” Dirk G. Brockstedt, PhD, executive vice president of research and development at Aduro, said in a news release.
“Gastric cancer is an immune-sensitive mesothelin-expressing tumor where PD-1 checkpoint inhibitors have shown some activity,” he said. “The combination of inducing an immune response through CRS-207, while simultaneously suppressing the cancer’s ability to evade the immune system through a PD-1 checkpoint inhibitor, has resulted in synergistic anti-tumor activity in pre-clinical studies. We aspire to reproduce this activity in the clinic in patients with gastric cancer.”
LADD is designed to allow the safe administration of Listeria by deleting two genes that are critical for the bacteria’s virulence, creating a weakened strain that expresses specific proteins from the tumor cells, according to a company webpage.
When the bacteria are engulfed by the dendritic cells of cancer patients, the tumor proteins are recognized as foreign, prompting tumor-killing T-cells to attack cancer cells with those particular proteins on their surface.
CRS-207 is currently being evaluated in malignant pleural mesothelioma and ovarian cancer patients in combination with standard-of-care chemotherapy. In the mesothelioma group, more than half of CRS-207 treated patients responded to the treatment, highlighting the therapeutic potential of this new Listeria-based immunotherapy.
