The U.S. Food and Drug Administration (FDA) has placed a partial hold on all clinical trials evaluating the LADD (Listeria-based immunotherapy construct) technology platform, pausing new patient enrollment. Those already undergoing therapy will continue with the treatment.
Announced in a news release by Aduro Biotech, the therapy’s developer, the partial hold came after the company had notified the FDA that one patient with metastatic pancreatic cancer developed gastrointestinal symptoms, and tested positive for Listeria in a blood sample.
The proprietary LADD platform uses modified Listeria bacteria engineered to work as agents that trigger strong immune responses to specific tumor antigens.
LADD is designed to allow the safe administration of Listeria by deleting two genes that are 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 bacteria are engulfed by the dendritic cells of cancer patients, the tumor proteins are recognized as foreign, spurring tumor-killing T-cells to attack cancer cells with those particular proteins on their surface.
Aduro is developing and testing this technology as a treatment for multiple cancers, including ovarian, lung, pancreatic, and prostate cancer, as well as glioblastoma and mesothelioma.
The mesothelioma trial is an open-label Phase 1b safety and efficacy study (NCT01675765), evaluating sequential administration of the cancer vaccine CRS-207, a weakened and genetically altered form of Listeria monocytogenes that activates immune cells to recognize mesothelin-expressing tumors. Aduro reports that it has enrolled 38 patients. The vaccine, in combination with Alimta (pemetrexed) and Platinol (cisplatin), is being assessed as a front-line therapy for malignant pleural mesothelioma adult patients.
Aduro is working with the FDA to lift the partial hold and resume new enrollment into its clinical trials with LADD-based agents. Based on feedback from the FDA, the company is revising study protocols to modify the antibiotic administration following treatment, extend patient surveillance, and exclude patients who are or will receive immune-supressive treatments or prosthetic devices.
Patients in studies who are already receiving a LADD-based agent, a therapy that began more than six months ago for some, will continue to receive treatment.
The patient who tested positive for Listeria was treated with intravenous antibiotics and showed no signs of the bacteria in subsequent blood tests.