On June 29, 2022 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products, reported an update on the Phase 1 clinical study evaluating ADXS-504, the company’s off-the-shelf neoantigen drug candidate, in patients with biochemically recurrent (early) prostate cancer that is being conducted at Columbia University Irving Medical Center (Press release, Advaxis, JUN 29, 2022, View Source [SID1234616358]). Karie Runcie, MD, assistant professor of medicine, and Mark N. Stein, MD, associate professor of medicine, in the division of hematology/oncology at Columbia University Vagelos College of Physicians and Surgeons, are the study’s principal and senior investigators, respectively.
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The Phase 1 open-label dose escalation study completed evaluation of the safety and tolerability of the first dose level (DL-1 1e7 CFU) and has initiated enrollment of the second dose level cohort (DL-2 1e8 CFU). In this cohort, ADXS-504 will be administered via infusion every four weeks for a total of six doses, followed by four additional maintenance doses every twelve weeks, in patients with biochemically recurrent prostate cancer, i.e., those with elevation of prostate-specific antigen (PSA) in the blood after radical prostatectomy or radical radiotherapy (external beam or brachytherapy) and who are not currently receiving androgen ablation therapy.
The preliminary clinical assessment of patients at the first dose level has shown that ADXS-504 monotherapy is safe and well tolerated. Clinical and immunogenicity data, including PSA values, for patients in both cohorts will be presented at a future medical conference.
ADXS-504 is a novel Lm-based immunotherapy, bioengineered to elicit T cell responses against 24 tumor antigens, including 14 peptide antigens derived from hotspot mutations in patients with prostate cancer and 10 peptide antigens derived from sequence-optimized tumor-associated antigens (TAAs) that are differentially expressed or overexpressed in prostate cancer. ADXS-504 is designed to express multiple tumor antigen targets, potentially leading to generation of a broad set of effector T cells that may enhance tumor control. Similar to Advaxis’s other Lm-based immunotherapies, ADXS-504 is expected to induce an innate immune response followed by the adaptive response and modification of the immunosuppressive tumor microenvironment (TME) by reducing regulatory T cells (Tregs) and myeloid-derived suppressor cell (MDSC) frequencies in the TME.
Dr. Runcie remarked, "Thus far, patients have only experienced mild and short-lived flu-like symptoms after the infusion of ADXS-504 at the first dose level. We look forward to collecting data at the second dose level to gain further insight into the safety and efficacy of this novel therapy."
Kenneth A. Berlin, President and Chief Executive Officer of Advaxis, said, "We are encouraged by the recent data regarding the safety profile of this new Advaxis’ HOT construct at the first dose level. As ADXS-504 is now being administered to healthier patients with longer life expectancies than to those evaluated in other Lm immunotherapy programs, it is important to have a relatively clean safety profile in this setting," he added. "Safety is an essential component of the regimen in this healthier population, which will now move on to dose level 2 at 1e8 CFU, a level that has also proven to be a relatively safe in our other Lm HOT-program," he concluded.