Immunotherapy Before and After Surgery

This study is an open-label, Phase 2 clinical trial investigating the efficacy and safety of a three-part immunotherapy regimen in combination with surgery for men with high-risk prostate cancer who have not yet undergone a prostatectomy. The immunotherapy consists of three components: N-803 (Nogapendekin Alfa Inbakicept): A soluble complex consisting of a modified human interleukin-15 (IL-15) variant bound to a human IL-15 receptor alpha subunit/human immunoglobulin G (IgG) Fc fusion protein. N-803 acts as a growth and activation factor for natural killer (NK) cells and effector and memory T-cells, enhancing their ability to kill cancer cells and stimulate an immune response. It is administered subcutaneously. ETBX-071 (hAd5 \[E1-, E2b-, E3-\]-PSA Vaccine): A replication-defective human adenovirus serotype 5 vector modified to encode human prostate-specific antigen (PSA). This vaccine is designed to induce a cell-mediated immune response against PSA-expressing prostate cancer cells. It is administered subcutaneously. M-CENK (Autologous Memory Cytokine-Enriched NK Cells): These are the patient's own NK cells that are collected through apheresis, expanded and activated ex vivo using cytokines (IL-12, IL-15, and IL-18) to enhance their cytotoxicity and IFN-γ production. The resulting M-CENK cells are then infused intravenously. Study Design: The study involves three main phases: Pre-surgery Immunotherapy: Participants receive N-803, ETBX-071, and M-CENK according to a specific schedule for six weeks before undergoing prostatectomy. Surgery: Participants undergo a radical prostatectomy. Post-surgery Immunotherapy: Following surgery, participants receive four cycles of the same immunotherapy regimen (N-803, ETBX-071, and M-CENK) over a 24-week period. Some participants may also receive external beam radiation therapy (EBRT) post-surgery at the discretion of the investigator. Endpoints: The study will assess several endpoints, including: Primary Endpoints: Event-free survival (EFS) and biochemical recurrence-free survival (bRFS) are the main measures of the treatment's effectiveness in preventing cancer recurrence. Secondary Endpoints: These include the rate of PSA reduction within six months post-surgery and safety assessments (adverse events, serious adverse events, changes in vital signs and laboratory tests). Exploratory Endpoints: These are additional measures to assess quality of life, sexual function, immune responses, and changes in the tumor microenvironment. Patient Selection: The study includes men with high-risk prostate cancer, defined by specific criteria related to PSA levels, Gleason score, and tumor stage. Participants must meet specific inclusion criteria and cannot have certain pre-existing conditions or prior treatments that might interfere with the study. Follow-up: Participants will be followed for up to five years after completing the treatment, with regular monitoring and assessments. This detailed description provides a more comprehensive overview of the study's design, methodology, and objectives.