The development of CRS207, manufactured by Aduro Biotech, has been discontinued following results from a phase 2 trial evaluating its efficacy in combination with Keytruda (Merck) for previously treated malignant plural mesothelioma.
The trial enrolled 10 patients who had received one or two prior lines of therapy and had progressed on standard chemotherapy (pemetrexed and platinum-based therapy). The patients received Keytruda plus CRS207 every three weeks for four cycles, after which Keytruda was administered once-every-three-weeks and CRS-207 was administered every six weeks. The primary endpoints were overall response rate, duration of response, the number of patients with at least stable disease, time to disease progression or death, and overall survival. Nine patients were evaluable for response, none of whom achieved a response to treatment. The disease control rate was 11% (1/9 with stable disease). Progression free survival ranged from 3.4 to 8.9 weeks. In addition, CRS207 moved through circulation very quickly. One patient had CRS-207 detected in the blood at 18-24 hours after the first dose. It had cleared by the next evaluation at Day 4; shedding samples (urine, fecal, and saliva) tested negative.
Based on this data and a comprehensive review of the clinical program, the development of CRS207 has been discontinued.
About Malignant Plural Mesothelioma
Malignant mesothelioma is a type of cancer that occurs in the thin layer of tissue that covers the majority of internal organs (mesothelium). Mesothelioma is divided into different types based on what part of the mesothelium is affected. Mesothelioma most often affects the tissue that surrounds the lungs (pleura). This type is called pleural mesothelioma.
About CRS207 and Keytruda
CRS-207 is a live, attenuated, double-deleted Listeria monocytogenes (LADD) engineered to stimulate immune response to mesothelin protein — which is over-expressed in a large variety of tumors, including mesothelioma — and trigger strong immune responses against this protein.
Keytruda is an immune checkpoint inhibitor meant to help the immune system recognize and fight cancer. It binds to a protein called PD-1 on immune T-cells, preventing interaction with its ligand, PD-L1, produced by cancer cells to avoid immune surveillance.
In prior phase I trials these immunotherapies showed promising response rates in mesothelioma patients, and a study in a lung cancer mouse model suggested that anti-PD-1 therapies like Keytruda could enhance CRS-207 responses.