Immunotherapy With N 803, ETBX-071, and M-CENK in Combination With Radiation for Participants With High-Risk Prostate Cancer.

This study (ResQ110B-PROS, IND 027158) is a Phase 2, open-label clinical trial designed to assess the safety and efficacy of a novel, multi-component treatment strategy for men with high-risk prostate cancer who are unsuitable for prostatectomy. The experimental treatment combines three investigational products with standard external beam radiation therapy (EBRT). The study is interventional, not observational.

The Investigational Products:

N-803 (nogapendekin alfa inbakicept): A soluble complex of an IL-15 variant bound to a human IL-15 receptor alpha subunit/human IgG1 Fc fusion protein. It acts as a growth and activation factor for NK cells and effector and memory T cells, aiming to stimulate the immune system's response to the cancer. Administered subcutaneously (SC).

ETBX-071 (hAd5 \[E1-, E2b-, E3-\]-PSA): A replication-defective human adenovirus serotype 5 (hAd5) vector modified to encode human prostate-specific antigen (PSA). This acts as a cancer vaccine, designed to generate an immune response targeting PSA-expressing prostate cancer cells. Administered subcutaneously (SC).

M-CENK (cytokine-induced memory-like NK cells): Autologous natural killer (NK) cells expanded and modified ex vivo using a cytokine cocktail (IL-12, IL-15, and IL-18) to enhance their cytotoxic activity and persistence. These cells are administered intravenously (IV).

Treatment Regimen:

The study employs a staged treatment approach:

Screening and Baseline Assessments: Participants undergo screening to confirm eligibility, including PSMA-PET scans, genomic testing, and PSA level assessment. Baseline assessments are collected before starting treatment.

Apheresis: Autologous peripheral blood mononuclear cells (MNCs) are collected from participants for the generation of M-CENK cells.

Pre-Radiation Immunotherapy: Participants receive N-803, ETBX-071, and M-CENK according to a specified schedule over a 6-week period. A targeted biopsy is performed before radiation.

Radiation Therapy (EBRT): Participants undergo EBRT (either a standard 2-week course or an extended 9-week course, as determined by the investigator).

Post-Radiation Immunotherapy: Following radiation, participants receive N-803, ETBX-071, and M-CENK for four 6-week cycles. Androgen deprivation therapy (ADT) may be initiated 6 months after completing radiotherapy.