Aduro, Merck to Begin Clinical Trial Assessing CRS-207, Keytruda Combo to Treat Worsening MPM

Aduro, Merck to Begin Clinical Trial Assessing CRS-207, Keytruda Combo to Treat Worsening MPM

Aduro Biotech has expanded its collaboration with Merck to include an additional Phase 2 trial to test a combination of Aduro’s immunotherapy, CRS-207, with Keytruda (pembrolizumab) in patients with malignant pleural mesothelioma (MPM) who progressed after prior treatment.

Aduro, based in Berkeley, California, announced a Phase 2 clinical collaboration with Merck in January 2017, testing the same combo therapy in gastric cancer patients.

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 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 many tumors, including mesothelioma and non-small cell lung cancer, as well as ovarian, endometrial, pancreatic and gastric cancers.

Researchers are now evaluating CRS-207 in MPM and ovarian cancer patients in combination with standard-of-care chemotherapy. More than half of mesothelioma patients treated with CRS-207 responded to the treatment, highlighting this new Listeria-based drug’s therapeutic potential.

“Data from our ongoing Phase 1 clinical trial of CRS-207 with standard chemotherapy as frontline treatment for malignant pleural mesothelioma have been very encouraging, including disease control in 94 percent of patients treated with the CRS-207/chemotherapy combination,” Dr. Natalie Sacks, Aduro’s chief medical officer, said in a news release. “Based on these clinical data, as well as data from preclinical studies that demonstrate synergistic activity of CRS-207 and anti-PD-1 therapy, we look forward to initiating a Phase 2 trial to evaluate the CRS-207/pembrolizumab combination in patients with malignant pleural mesothelioma who have failed prior treatment.”

The multicenter, open-label, single-arm Phase 2 trial is designed to evaluate the safety and efficacy of CRS-2017 plus Keytruda in up to 35 MPM patients who failed one or two prior lines of therapy.

LADD is designed to allow the safe administration of Listeria by deleting two genes 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 dendritic cells of cancer patients engulf the bacteria, the tumor proteins are recognized as foreign, prompting tumor-killing T-cells to attack cancer cells with those particular proteins on their surface.

MPM, which affects the thin balloon-shaped lining of the lungs, is the most common form of this mesothelioma. About 13,000 new cases of MPM appear annually in the United States, the European Union and Japan. MPM is an aggressive disease with a poor prognosis. Most MPM patients are not candidates for surgical resection, the company says, and no approved therapy currently exists for second- or third-line treatment of MPM.

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