The U.S. Food and Drug Administration (FDA) has lifted a partial hold placed on all Aduro’s clinical trials evaluating the LADD technology platform, a new Listeria-based cancer vaccine. These studies, including one in mesothelioma patients, will now resume patient enrollment.
The FDA placed a partial hold on trial enrollment on Oct. 24, after a patient with metastatic pancreatic cancer treated with the LADD-based vaccine developed gastrointestinal symptoms and tested positive for Listeria in a blood sample. The patient was successfully treated with antibiotics.
“We are pleased to come to a rapid agreement with the FDA to resume new patient enrollment in our LADD clinical studies,” Stephen T. Isaacs, chairman, president and CEO of Aduro Biotech, said in a press release. “With slight protocol modifications implemented, we remain on track to initiate a Phase 2 clinical study using our LADD-based therapy CRS-207 in combination with an anti-PD-1 compound for patients with mesothelioma in the first half of 2017.”
Under the terms of its agreement, Aduro modified the protocol of trials assessing LADD-based immunotherapy to extend patient surveillance, exclude patients with prosthetic devices that cannot be easily removed, and to include guidance for administering prophylactic antibiotics following treatment in patients receiving immunosuppressive therapies.
Aduro’s LADD platform uses weakened Listeria bacteria, which has been engineered to produce certain cancer proteins and work as a cancer vaccine. The engineered bacteria lacks two genes that are required for its virulence, creating a weakened strain that can be administered to patients.
The expression of certain cancer proteins induces a strong immune response toward cancer cells, Aduro reports on the company’s website. Following injection into patients, the bacteria are recognized as foreign and engulfed by dendritic cells — the body’s first line of defense. These cells then have the ability “present” the bacteria proteins to certain T-cells, which attack cancer cells with those particular proteins on their surface.
In mesothelioma patients, Aduro has been testing the mesothelin cancer protein. This LADD-based immunotherapy is currently in an open-label Phase 1b trial (NCT01675765) evaluating the safety and immune response of the CRS-207 vaccine as front-line therapy for adults with malignant pleural mesothelioma. A total of four CRS-207 treatments (two prime and two booster vaccinations) are being given participants, in addition to Alimta (pemetrexed) and Platinol (cisplatin) standard chemotherapy.