Recent findings from Phase 2 clinical trials indicated that CRS-207 had only low clinical activity, and these studies were terminated. But the treatment’s safety and activity are still being investigated in Phase 2 clinical trials, in combination with other anti-cancer treatments for patients, with pancreatic cancer.
CRS-207 belongs to a family of products on Aduro’s so-called LADD platform, which uses Listeria bacteria to activate strong immune responses against specific tumor-associated antigens (TAAs). An antigen is a substance that is not normally present in the body and that can trigger an immune response.
How CRS-207 works
The LADD platform (live, attenuated double-deleted Listeria) was based on proprietary attenuated strains of Listeria monocytogenes engineered to express TAAs and induce specific and targeted immune responses. Genes that might harm patients were deleted from the bacteria’s genome, so that it might be given to patients safely as a treatment without causing infection or sickness.
CRS-207 was thought to be likely to stimulate an immune response against mesothelin, a TAA that is overproduced by some tumors, including mesothelioma and pancreatic, ovarian, gastric and lung cancers. Mesothelin, which also helps cancer cells spread, is found only in limited amounts in normal tissues.
Aduro has since stopped developing the LADD platform and is now focusing on two other immunotherapy platforms: STING and B-select.
CRS-207 in clinical trials
CRS-207 was evaluated in several clinical trials, in combination with other treatments, in people with different cancer types.
A Phase 2 study (NCT03175172) aimed at recruiting 35 patients to assess the safety and effectiveness of CRS-207 along with Keytruda (pembrolizumab) in adults with malignant pleural mesothelioma who had not responded to previous anti-cancer treatments. The trial was intended to measure the number of participants who showed a complete or partial response, the time from the first dose of treatment until disease progression or death, and any improvement in lung function. The trial was terminated due to low enrollment and lack of clinical activity. Results were presented at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium. The treatment combination was safe, but no clinical efficacy was observed.
Similar results were found in another Phase 2 trial (NCT03122548), which aimed at recruiting 79 participants with recurrent or metastatic gastric, gastroesophageal, or esophageal cancers. That study, which aimed to assess the safety and effectiveness of the same combination of therapies against these cancers, also ended early due to low enrollment, and a lack of efficacy.
In a two-part Phase 1/2 study (NCT02575807) researchers tested CRS-207, epacadostat, and Keytruda in 126 women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer. That trial was intended to investigate whether different combinations of the three treatments could slow cancer growth and extend the lifespan of patients. This study also was terminated due to low enrollment and lack of clinical activity.
Now, two new Phase 2 studies (NCT03190265 and NCT03006302) will evaluate the safety and clinical activity of CRS-207 combined with other anticancer treatments in people with pancreatic cancer. Those two trials are currently recruiting participants at a single site in Maryland.
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