MPM is the most prevalent form of mesothelioma disease, with about 3,000 new cases a year in the United States. MPM currently has a poor prognosis, and most patients are not candidates for surgical resection.
The multicenter Phase 2 study will evaluate the safety and efficacy of Aduro’s immunotherapy product CRS-207 in combination with Keytruda (pembrolizumab) in 35 adults with MPM, whose disease progressed after one or two prior treatments. The primary goal is to assess the objective response rate, or the proportion of patients with complete or partial response to the new therapy.
CRS-207 was designed to contain the tumor-associated antigen mesothelin, which is overproduced in many cancers including mesothelioma and gastric cancer. The product is Aduro’s lead LADD (live, attenuated double-deleted) candidate, engineered with listeria bacteria to trigger specific immune responses to specific tumor antigens.
The study results from a clinical collaboration between Aduro and Merck that was announced in January 2017. Besides investigating the potential therapeutic effect in MPM, the combination of CRS-207 with Keytruda will also be tested in gastric cancer patients.
“We are excited to initiate this Phase 2 trial to evaluate the combination of CRS-207 and pembrolizumab, an anti-PD-1 therapy, which we believe has the potential to be a synergistic combination therapy for patients with MPM,” Dr. Natalie Sacks, chief medical officer at Aduro, said in a press release. “Mesothelioma is an aggressive cancer with a poor prognosis and limited treatment options; currently, there are no FDA-approved therapies indicated for second- or third-line treatment.”
A previous Phase 1b study (NCT01675765) evaluated CRS-207 alone and in combination with standard chemotherapy in 36 patients with newly-diagnosed MPM. The treatment controlled the disease in 94 percent of patients, including 3 percent who had a complete response, and 56 percent who experienced partial responses. The remaining 36 percent achieved stable disease.
Conversely, treatment with two doses of CRS-207 prior to chemotherapy reduced tumor size in 31 percent of patients and induced other changes, including an increase in immune cell types that researchers believe play a key role in immunotherapy. These results supported the clinical activity of single-agent CRS-207.