FDA Slaps Partial Hold on Bay Area Firm Aduro Biotech's Cancer Vaccine Trial

Published: Oct 25, 2016

FDA Slaps Partial Hold on Bay Area Firm Aduro Biotech's Cancer Vaccine Trial October 24, 2016
By Mark Terry, BioSpace.com Breaking News Staff

The U.S. Food and Drug Administration (FDA) placed a partial hold on Berkeley, Calif.-based Aduro Biotech ’s LADD trials.

Aduro’s LADD technology is a method of engineering the bacteria Lysteria monocytogenes into therapeutics that stimulate targeted immune response to specific tumor antigens. The FDA didn’t specifically halt the trial, but paused new patient enrollment.

The FDA hold was initiated after a blood culture sample on an indwelling port of a metastatic pancreatic cancer patient tested positive Listeria. The positive Listeria is suspected of being CRS-207. The patient presented with gastrointestinal symptoms, and was treated with intravenous antibiotics. As a result, subsequent blood cultures didn’t show signs of Listeria and the patient is recovering.

All patients in the trial are continuing to receive treatment except one, who is on a pacemaker. The company stated, “Aduro is working with the FDA to lift the partial hold so as to resume new patient enrollment in its LADD clinical trials. The company is revising study protocols in accordance with feedback from the agency, including the modification of antibiotic administration following treatment, extended patient surveillance, and, as a pre-emptive measure, exclusion of patients who are on or will receive certain immune-suppressive treatments or who have certain prosthetic devices.”

The LADD program uses live, attenuated double-deleted strains of Listeria monocytogenes that have been engineered to stimulate an innate immune response. They have also been engineered to express tumor-associated antigens, which causes the T-cells to attack specific tumors. CRS-207 is one of a group of product candidates in the LADD program that expressed the tumor-associated antigen mesothelin, which is over-expressed in various cancers, including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.

The company has two other separate platform technologies, STING pathway activators and B-select monoclonal antibodies. The partial hold does not affect either of those platform programs.

Aduro recently presented two posters at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference in New York. The first provided preclinical data in its LADD program showing positive changes in the tumor microenvironment and induction of a tumor-specific immune response. The second poster discussed its STING (Stimulator of Interferon Genes) Pathway Activator immunotherapy program. Both presentations indicated that the addition of a PD-1 blockade demonstrated significant antitumor efficacy.

“These preclinical data demonstrate the underlying mechanisms by which our LADD and STING immunotherapy platforms activate the immune system and induce robust innate immunity, facilitating a change in the tumor microenvironment which results in effective destruction of cancer cells in several preclinical models,” said Thomas Dubensky, Jr., Aduro’s chief scientific officer, in a statement. “Importantly, the combination data are even more impressive, showing increased efficacy when our LADD and STING platforms are combined with an anti-PD1 checkpoint inhibitor to combat the tumor’s ability to hide from the immune system. These data support our strategy to combine our immunotherapy regimens with checkpoint inhibitors for greater anti-tumor activity, looking toward the ultimate goal of better, more effective patient care.”

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