This Phase 2 clinical trial is testing a new immunotherapy combination (N-803, ETBX-071,M-CENK) for men with high-risk prostate cancer before and after prostate surgery. Thegoal is to see if this treatment improves cancer outcomes and is safe.
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.
Drug: N-803
A subcutaneous injection of an IL-15 superagonist.
Drug: ETBX-071
A subcutaneous injection of a prostate-specific antigen (PSA) adenovirus vaccine.
Drug: M-CENK
An intravenous infusion of the patient's own NK cells that have been expanded and
activated in a laboratory.
Inclusion Criteria:
- Age: Must be 18 years or older.
- Consent: Able to understand and provide signed informed consent that complies with
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
- Diagnosis: Histologically confirmed prostate adenocarcinoma (unless a local
pathologist's report shows consistent findings).
- Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1.
- Life Expectancy: Must have a life expectancy of at least 10 years.
- Germline Testing: Must have undergone germline testing at the time of initial
diagnosis (and at recurrence, if applicable).
- Metastasis: No evidence of soft tissue disease metastasis (visceral or lymph nodes)
on CT/MRI scan.
- Autoimmune Disease: No active or organ-threatening autoimmune disease.
- High-Risk Prostate Cancer: Must have high-risk or very high-risk prostate cancer
according to 2024 NCCN guidelines (PSA >20 ng/mL, or Gleason Grade Group ≥4, or
≥cT3a).
- Adequate Hematologic and Organ Function: Must meet specific criteria for absolute
neutrophil count (ANC), lymphocyte count, platelet count, hemoglobin, INR or aPTT,
AST, ALT, and alkaline phosphatase levels. Certain exceptions are made for
participants with liver or bone metastases.
- Ability to Attend Visits: Must be able to attend required study visits and return
for adequate follow-up.
- Contraception: If male and not surgically sterile, must agree to use effective
contraception for up to 7 months after treatment.
Exclusion Criteria:
- Prior Prostate Treatments: Prior surgical, cryotherapy, or high-intensity focused
ultrasound treatment for prostate cancer; prior orchiectomy or hormonal therapy
(GnRH agonists, NSAA).
- Prior Anti-Androgen Therapy: Prior treatment with first-generation or
second-generation androgen receptor (AR) inhibitors (e.g., bicalutamide, flutamide,
nilutamide, cyproterone acetate; enzalutamide, apalutamide, or darolutamide).
- Organ Transplantation: Receipt of any organ transplantation (excluding those that
don't require immunosuppression, like corneal or hair transplants).
- Corticosteroid Use: Chronic systemic corticosteroid administration (>14 days within
28 days before treatment initiation) except for topical, inhaled, or nasal
corticosteroids.
- Active Autoimmune Disease: Active autoimmune disease (e.g., Addison's disease,
Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome,
scleroderma, myasthenia gravis, Goodpasture syndrome, or active Graves' disease).
Exceptions are made for those with a history of autoimmune disease that did not
require systemic immunosuppression and does not threaten vital organ function.
- Medications Affecting Urinary Symptoms or PSA: Use of medications for urinary
symptoms (5-alpha reductase inhibitors, alternative medications known to alter PSA
levels) within 28 days prior to study initiation.
- Recent Major Surgery or Systemic Therapy: Major surgery or systemic therapy
(including investigational therapies) within 28 days prior to study initiation.
- Allergic Reactions: History of allergic reactions to compounds with similar chemical
or biological composition to the study drugs.
- Significant Cardiovascular or Cerebrovascular Disease: Clinically significant
cardiovascular/cerebrovascular disease (e.g., stroke, myocardial infarction,
unstable angina, congestive heart failure, serious cardiac arrhythmia, or
uncontrolled hypertension) within six months prior to the first planned dose of
study drugs.
- Intercurrent Medical Illness: Serious intercurrent medical illness that would
interfere with participation.
- Infections: Active HIV, hepatitis B or C infection.
- Live Attenuated Vaccines: Administration of a live, attenuated vaccine within three
weeks before study entry or anticipation that such a vaccine will be required during
the study.
- Inability to Comply: The investigator deems the participant unable or unwilling to
comply with study requirements.
Not Provided
Joseph Ward
3236933913
joseph.ward@immunitybio.com
Deana Martz
3234936386
deana.martz@immunitybio.com
Bruce Brown, Study Chair
ImmunityBio, Inc.