Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer

NCT04989946 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: 2021-0575Protocol Version 12/3/2024W81XWH2110270A534260P50CA269011-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (4)

• Pathological Complete Response Rate (pCR)

  The pathological complete response will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis.

  at prostatectomy (up to 3 months)

• Minimal Residual Disease (MRD) Rate

  The MRD rate will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis.

  at prostatectomy (up to 3 months)

• Incidence of Adverse Events

  Adverse events will be evaluated using the most recent version of the Common Terminology Criteria for Adverse Events (CTCAE).

  up to 15 months

• Toxicity Rates

  Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated for each study arm and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.

  up to 15 months

Secondary Outcomes (3)

• Progression-Free Survival (PSA) at 1-year

  up to 15 months on study (1 year after prostatectomy)

• Residual Cancer Burden (RCB)

  at prostatectomy (up to 3 months)

• Median Progression-Free Survival

  up to 39 months

Other Outcomes (7)

• Number of AR-specific Th1-biased T-cell responses

  up to 15 months on study (1 year after prostatectomy)

• Change in levels of prostate tissue-infiltrating CD8+T cells

  baseline, month 3

• Change in levels of AR-specific tumor-infiltrating CD8+T cells

  baseline, month 3

Study Arms (5)

Arm 1: Degarelix

ACTIVE COMPARATOR

\- Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57

Drug: Degarelix; Drug: FLT PET/CT

Arm 2: Degarelix and pTVG-AR

EXPERIMENTAL

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71

Drug: Degarelix; Biological: pTVG-AR; Drug: FLT PET/CT

Arm 3: Degarelix and pTVG-AR and Nivolumab

EXPERIMENTAL

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Nivolumab 240 mg IV administered at days 29, 43, 57 and 71

Drug: Degarelix; Biological: pTVG-AR; Drug: Nivolumab; Drug: FLT PET/CT

Arm 4: Degarelix and pTVG-AR and Cemiplimab

EXPERIMENTAL

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64

Drug: Degarelix; Biological: pTVG-AR; Drug: Cemiplimab

Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab

EXPERIMENTAL

* Degarelix 240 mg s.c. day 29, 80 mg s.c. day 57 * pTVG-AR (100 µg) administered intradermally (i.d.) at days 1, 8, 15, 22, 29, 43, 57 and 71 * Cemiplimab 350 mg IV administered at days 1, 22, 43 and 64 * Fianlimab 1600 mg IV administered at days 1, 22, 43 and 64

Drug: Degarelix; Biological: pTVG-AR; Drug: Cemiplimab; Drug: Fianlimab

Interventions

Degarelix DRUG

standard Gonadotropin-releasing hormone (GnRH) antagonist

Arm 1: Degarelix; Arm 2: Degarelix and pTVG-AR; Arm 3: Degarelix and pTVG-AR and Nivolumab; Arm 4: Degarelix and pTVG-AR and Cemiplimab; Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab

pTVG-AR BIOLOGICAL

DNA vaccine encoding androgen receptor ligand-binding domain

Arm 2: Degarelix and pTVG-AR; Arm 3: Degarelix and pTVG-AR and Nivolumab; Arm 4: Degarelix and pTVG-AR and Cemiplimab; Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab

Nivolumab DRUG

Nivolumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.

Also known as: Opdivo

Arm 3: Degarelix and pTVG-AR and Nivolumab

Cemiplimab DRUG

Cemiplimab is a human PD-1 blocking antibody approved for the treatment of patients with non-small cell lung cancer, cutaneous squamous cell carcinoma, and locally advanced basal cell carcinoma.

Also known as: Libtavo

Arm 4: Degarelix and pTVG-AR and Cemiplimab; Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab

Fianlimab DRUG

Lymphocyte activation gene-3 (LAG-3) is a protein that is upregulated on activated CD4+ and CD8+ T cells following T-cell receptor engagement. Binding of LAG-3 to MHC II on professional antigen-presenting cells suppresses the proliferation, activation, and cytokine secretion of T cells. Fianlimab is a human IgG4 antibody to lymphocyte activation gene-3 (LAG-3) that blocks LAG-3/MHC II-mediated T-cell inhibition.

Also known as: REGN3767

Arm 5: Degarelix and pTVG-AR and Cemiplimab and Fianlimab

FLT PET/CT DRUG

Arms 1-3 only, FLT PET/CT scan at baseline (within 1-6 days of Day 1) and Day 43

Also known as: 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) positron emission tomography (PET) /computed tomography (CT)

Arm 1: Degarelix; Arm 2: Degarelix and pTVG-AR; Arm 3: Degarelix and pTVG-AR and Nivolumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Patients must be considered candidates for prostatectomy as per standard of care
• High-risk patients for recurrent disease, with high risk defined based on one of the following criteria:
• Gleason score 7 and baseline serum prostate specific antigen (PSA) \> 20 ng/mL
• Gleason score \> 7
• Life expectancy of at least 12 months at screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, renal and liver function as evidenced by the following within 4 weeks of day 1:
• Absolute neutrophil count (ANC) \> 1000 / mm3
• HgB \> 9.0 gm/dL independent of transfusion
• Platelets \> 100,000 / mm3
• Creatinine \< 2.0 mg/dL
• Aspartate aminotransferase (AST), Alanine transaminase (ALT) \< 2.5 x institutional upper limit of normal (ULN)
• Total bilirubin \< 2x institutional ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is \>2x ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible)
• No known history of HIV 1 and 2, HTLV-1, or active Hepatitis B or Hepatitis C

You may not qualify if:

• Small cell or other variant (non-adenocarcinoma) prostate cancer histology
• Prior treatment for prostate cancer, including androgen deprivation therapy (ADT), orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide
• Prior radiation to the prostate
• Patients may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than the treatment-prescribed androgen deprivation therapy
• Treatment with any of the following medications while on study is prohibited, washout period not required except as indicated:
• Systemic corticosteroids (at doses over the equivalent of 10 mg prednisone daily) - not permitted within 3 months of registration; inhaled, intranasal or topical corticosteroids are acceptable
• PC-SPES
• Herbal supplements that have been shown to modulate testosterone or androgen signaling (e.g. Saw Palmetto) are not allowed while on study
• Megestrol
• Ketoconazole
• α-reductase inhibitors - patients already taking 5-α-reductase inhibitors prior to 28 days prior to registration may stay on these agents throughout the course of therapy, but these should not be started while patients are on study
• Diethylstilbesterol
• Any other non-study hormonal agent or supplement being used with the intent of cancer treatment
• Major surgery within 4 weeks of registration is prohibited
• Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within 6 months of registration

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• United States Department of Defense: collaborator
• Regeneron Pharmaceuticals: collaborator
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

Related Publications (1)

• Jarrard D, Eickhoff J, Kyriakopoulos CE, Jeon D, Tonelli TP, Johnson L, Huang W, McNeel DG. Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancer. J Immunother Cancer. 2026 Mar 4;14(3):e013790. doi: 10.1136/jitc-2025-013790.

  PMID: 41781018 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Nivolumab; cemiplimab; alovudine; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Christos Kyriakopoulos, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a randomized, open-label, single-institution phase 1/2 trial designed to evaluate the immunological and clinical effect of pTVG-AR, a DNA vaccine encoding AR, given with or without T-cell checkpoint blockade in combination with standard androgen deprivation for patients with newly diagnosed high-risk prostate cancer.

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 4, 2021
• Study Start: December 16, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 28, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)