IL-15 Superagonist With or Without Vaccine in Biochemically Recurrent Prostate Cancer After Previous Stereotactic Body Radiation Therapy

NCT07686380 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10002231002231-C
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Biochemically recurrent prostate cancer (BCR) occurs when prostate-specific antigen (PSA) levels in the blood rise after surgery or radiation. BCR affects 30,000 to 50,000 men each year. Researchers want to know if a drug (N-803) alone or combined with a vaccine (ETBX-071) can reduce PSA in BCR prostate cancer after radiation. Objective: To test a study drug alone and combined with a vaccine in people with BCR prostate cancer who have been treated with targeted radiation to areas of recurrent prostate cancer in the past. Eligibility: People aged 18 years and older with BCR prostate cancer who have previously undergone treatment with stereotactic body radiation therapy (SBRT). Design: Participants will be screened. They will have a physical exam with blood tests. They will have tests of their heart and kidney function. They will have 3 different imaging scans of their tumors. N-803 is injected under the skin of the abdomen. ETBX-071 is injected under the skin of thigh. Participants will be divided into 2 groups: 1 group will get N-803 alone; 1 group will get both N-803 and ETBX-071. The drug or drugs will be given on the first day of 21-day treatment cycles. Participants will have 8 treatment cycles. Participants will have a follow-up visit 3 weeks after their last dose of the study drugs. Blood tests and all 3 imaging scans will be repeated. Follow-up visits will continue every 4 to 8 weeks for 5 years. These visits will include a positron emission tomography (PET) scan every 6 months.

Conditions

Recurrent Prostate Cancer; Prostate Cancer

Keywords

Recurrent Prostate Cancer; IL-15 Superagonist; N-803; ETBX-071; PSA Vaccine

Outcome Measures

Primary Outcomes (1)

• Efficacy of N-803 alone or with ETBX-071 vaccine

  PSA30 response- defined as a \>= 30% reduction in PSA from PSA at C1D1 of immunotherapy (comparing C1D1 PSA to timepoints during and after immunotherapy). The fractions with PSA30 response will be reported along with a 95% confidence interval, separately for the two randomized treatment groups.

  D1 of each cycle of immunotherapy, at the end of treatment and every 4-8 weeks during follow-up until up to 5 years

Secondary Outcomes (6)

• Duration of PSA50 response

  D1 of each cycle of immunotherapy, at the end of treatment and every 4-8 weeks during follow-up until up to 5 years

• Time to PSA progression

  D1 of each cycle of immunotherapy, at the end of treatment and every 4-8 weeks during follow-up until up to 5 years

• PSA doubling timing

  D1 of each cycle of immunotherapy, at the end of treatment and every 4-8 weeks during follow-up until up to 5 years

• Proportion of participants with 30% PSA decline receiving immunotherapy treatment after SBRT

  D1 of each cycle of immunotherapy, at the end of treatment and every 4-8 weeks during follow-up until up to 5 years

• Safety

  C1D1 of each cycle during immunotherapy and at the end of treatment

Study Arms (2)

N803

EXPERIMENTAL

N803

Drug: N-803; Radiation: 18F-DCFPyL

N803+ETBX-071 vaccine

EXPERIMENTAL

N803+ETBX-071 vaccine

Drug: N-803; Drug: ETBX-71 Vaccine; Radiation: 18F-DCFPyL

Interventions

N-803 DRUG

15 mg/kg subcutaneous on Day 1 of every 3-week cycle for up to 8 cycles

N803; N803+ETBX-071 vaccine

ETBX-71 Vaccine DRUG

The dose to be injected is 5(SqrRoot) 10\^11 viral particles (VP) per 1 mL. Injected subcutaneously on Day 1 of every 3-week cycle for a total of up to 8 cycles

N803+ETBX-071 vaccine

18F-DCFPyL RADIATION

Single IV dose of 18F-DCFPyL by bolus injection. The target administered activity will be 6.5 mCi with a lower limit of 6 mCi

N803; N803+ETBX-071 vaccine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathological confirmation of prostate adenocarcinoma by the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center prior to the study treatment initiation. If no pathologic specimen is available, participants may enroll with a pathologist s report showing a histologic diagnosis of prostate adenocarcinoma and a clinical course consistent with the disease from any outside site.
• Biochemically recurrent prostate cancer, defined as PSA over 0.8 ng/ml following radical prostatectomy or \>= 2 ng/ml above the nadir following definitive radiotherapy or definitive radiotherapy (including brachytherapy) for localized prostate cancer.
• Participants must be at least 1 year removed from definitive local therapy before the study treatment initiation.
• Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation.
• Hepatic function eligibility parameters: Bilirubin (total and direct) \<= upper limit of normal (ULN) (OR in participants with Gilbert s syndrome, a total bilirubin \<= 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) \<= 1.5 times upper limit of normal.
• Adequate renal function defined by a calculated creatinine clearance \> 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
• ECOG performance score 0-1.
• No other active malignancies within the 36 months prior to the study treatment initiation (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder).
• years of age or older.
• Individuals must agree to use effective contraception (barrier, vasectomy and/or abstinence) for the duration of study therapy and for four months after the last treatment administration. Individuals with partners with birthing potential will be recommended that their partner use a highly effective contraception (includes use of oral, injected or implanted hormonal methods of contraception, placement of certain intrauterine devices (IUD) or intrauterine systems (IUS), hysterectomy, oophorectomy, salpingectomy.
• Individuals must agree to not donate sperm during the restricted period (for the duration of study therapy and for four months after the last dose of study treatment).
• Negative CT scan/ Magnetic resonance imaging (MRI) for evidence of soft tissue metastasis (visceral or lymph node).
• Negative Tc99 for evidence of bone disease.
• Participants must have had prior SBRT to PSMA+ findings beyond the prostate and have had a documented 25% or more PSA rise from post-SBRT nadir
• Baseline testosterone \>= 100 ng/dl.

You may not qualify if:

• Immunocompromised status due to:
• Human immunodeficiency virus (HIV) seropositivity
• HBV or HCV seropositivity
• Other immunodeficiency diseases
• Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed. Participants with diabetes type I, vitiligo, or alopecia are allowed.
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
• Chronic administration (defined as daily or every other day for continued use \> 14 days) of systemic corticosteroids within 28 days before the study treatment initiation. Note: Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
• Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g., phytoestrogens and saw palmetto) within 28 days prior to the study treatment initiation.
• Major surgery within 28 days prior to study treatment initiation.
• Systemic therapy, including any investigational therapy within 28 days prior to the study treatment initiation.
• Radiation therapy within 14 days prior to the study treatment initiation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.
• Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (\< 6 months prior to the first planned dose of study drugs), myocardial infarction (\< 6 months prior to the first planned dose of study drugs), or any of the following at time of enrollment: unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II), serious cardiac arrhythmia, or uncontrolled hypertension (SBP\>170/ DBP\>105).
• Serious intercurrent medical illness evaluated by medical history and physical exam that would interfere with participant's ability to carry out the treatment program.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ALT-803; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Melissa L Abel, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy R Hankin, P.A.-C

CONTACT

(240) 858-3149; amy.hankin@nih.gov

Melissa L Abel, M.D.

CONTACT

(240) 447-5353; melissa.abel@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 7, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): January 30, 2029
• Study Completion (Estimated): January 30, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.@@@@@@
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.@@@@@@

Locations

US (1)