FDA Grants Orphan Drug Designation for CRS-207 in Mesothelioma

The cancer vaccine CRS-207, a novel immuno-oncology product candidate for the treatment of mesothelioma, is receiving the greenlight from the US Food and Drug Administration (FDA). On March 24, 2015, it granted orphan drug status for this product. The FDA previously granted orphan designation to CRS-207 and GVAX Pancreas for the treatment of pancreatic cancer.

CRS-207 is being developed by Aduro Biotech and it is part of the company's family of product candidates based on its live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform. This platform reportedly induces a potent innate and T-cell mediated adaptive immune response. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is overexpressed in many cancers, including mesothelioma and pancreatic cancer. It is also overexpressed in non-small cell lung (NSCLC), ovarian cancer, endometrial cancer, and gastric cancer.

Dirk Brockstedt, PhD, who is a senior vice president of research and development at Aduro Biotech, Berkeley, Calif., said this new designation by the FDA is an important step, and the combination of CRS-207 with chemotherapy may offer the promise of a potential new therapeutic regimen for patients suffering from mesothelioma. Brockstedt said the company plans to report additional data from the ongoing phase 1b study using CRS-207 within the next 7 months.

CRS-207 is being developed for patients with malignant pleural mesothelioma who have not received prior therapy and are not eligible for surgical resection. Patients are currently being enrolled in a single-arm phase 1b clinical trial of CRS-207 in combination with standard-of-care chemotherapy.

Interim results from this trial were presented at the International Mesothelioma Interest Group Conference in October 2014, and demonstrated a 94% rate of disease control (partial response and stable disease) for the 16 treated, evaluable patients with response data. The interim results showed 75% of patients (12 out of 16) had confirmed partial responses, and 19% (3 out of 16) experienced stable disease. At the time of the presentation, estimated progression-free survival (PFS) was 7.5 months, with one patient on study for more than 19 months. Based on these encouraging results, Aduro Biotech opened an expansion cohort of up to a total of 40 patients and expects to finish enrollment in the study by December of this year.

Mesothelioma is a form of cancer that affects the smooth layer of mesothelial cells that surround the chest, lungs, heart and abdomen. Malignant pleural mesothelioma (MPM) is the most common form of this disease and accounts for approximately 3,000 cases a year in the United States. MPM is an aggressive disease with a poor prognosis and the majority of MPM patients are not candidates for surgical resection. Based on prior studies, expected median PFS is 5.7 months and overall survival is 12.1 months with combination pemetrexed and cisplatin chemotherapy. The tumor-associated antigen mesothelin is overexpressed in almost all cases of mesothelioma.