A phase I study of ADXS-504, a cancer type specific immunotherapy, for patients with biochemically recurrent prostate cancer.
Authors: Runcie Karie , Dallos Matthew , Khan Shaheer , Gray Jillian , Marco Paul , Ping Lucie , LaTourette Debra , Anderson Christopher B. , Spina Catherine S. , Yu James B. , Deutsch Israel , Sheeri Sumitra , Gutierrez Andres A. , Stein Mark N. 
Published: June 2022

TPS5115 Background: Roughly 20%-30% of prostate cancer patients experience biochemical recurrence (BCR), rising prostate-specific antigen (PSA) levels, after definitive therapy with radical prostatectomy (RP) or radiation therapy (RT). The optimal therapy and timing of treatment for BCR is unknown, however, for patients who are not eligible for salvage radiation, androgen deprivation therapy (ADT) is the standard first-line treatment. ADT is an effective therapy but has many acute and long-term toxicities. Novel strategies to reduce ADT exposure and prolong disease control are needed. ADXS-504 is a live attenuated Listeria monocytogenes (Lm)-based immunotherapy consisting of a truncated nonhemolytic fragment of listeriolysin O (tLLO) fused to a total of 24 tumor associated antigens (TAA). ADXS-504 was designed so that nearly 20% of patients with BCR cancer will express at least one of the targeted hotspot mutation peptide antigens and that >90% will express at least one of the TAAs targeted by the sequence-optimized TAA peptide antigens. By combining these shared, commonly expressed antigen targets into a single Lm-based immunotherapy, ADXS-504 provides the potential for a potent, disease-specific approach to treating patients with prostate cancer. In addition to the generation of antigen-specific T cell responses, treatment with Lm-based immunotherapies has been shown to reprogram the tumor microenvironment (TME), by reducing the frequencies and function of immunosuppressive regulatory T cells and myeloid-derived suppressor cells within the TME. A pre-clinical murine model showed that a proto-type Lm-construct could reduce the number of metastases after removal of the primary tumor by eliminating residual tumor cells. We hypothesize that ADXS-504 is safe and promotes anti-tumor immune responses that may delay or prevent the use of ADT in castration sensitive prostate cancer. Methods: This is an open-label dose-escalation phase I trial of ADXS-504 in patients with BCR of prostate cancer previously treated with RP or RT. The study will enroll up to 18 subjects with BCR with a PSA ≥ 0.3 and a PSADT ≥ 4 months without evidence of metastatic disease on traditional CT imaging and bone scans. ADXS-504 will be given by IV every 4 weeks level for 6 study treatments, followed by maintenance therapy given every 12 weeks for 4 doses for overall total of 10 doses of study treatment. DLTs will be evaluated over the first 28 days of treatment. PSA response, PSADT, and adverse events will be summarized. The Kaplan- Meier method will be used to estimate time to PSA progression and rPFS. Immunologic activity will be evaluated by ELISpot analysis, flow cytometry, and multiplex assays and blood samples will be collected for gene sequencing analysis. The study is currently open to enrollment. Clinical trial information: NCT05077098.