Trial Outcomes & Findings for PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer (NCT NCT02933255)

Last Updated: 2024-05-31

Results Overview

Clinically important immune-related adverse events were defined as grade 3 or above inflammation requiring steroids or anti cytokine therapy or not resolving to grade 1 or less within 28 days. These immune-related adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe, grade 4 is life-threatening, and grade 5 is death related to adverse event.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

From treatment start throughout study completion, an average of 1.4 years.

Results posted on

2024-05-31

Participant Flow

Participant milestones

Participant milestones
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Overall Study STARTED	12	12
Overall Study Follow Up Period Completed	11	12
Overall Study COMPLETED	11	12
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Overall Study Discontinued due to study closure.	1	0

Baseline Characteristics

PROSTVAC in Combination With Nivolumab in Men With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Total n=24 Participants Total of all reporting groups
Age, Categorical >=65 years	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	71.48 years STANDARD_DEVIATION 7.42 • n=5 Participants	60.93 years STANDARD_DEVIATION 6.53 • n=7 Participants	66.2 years STANDARD_DEVIATION 8.71 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: From treatment start throughout study completion, an average of 1.4 years.

Population: \*2 out of 7 immune related adverse events (irAEs) occurred during administration of both ipilimumab and nivolumab, before a protocol amendment was performed and eliminated ipilimumab from the study treatment.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 3 irAE hepatitis (alanine aminotransferase (ALT) increase)	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 4 irAE myositis (CPK increase)	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 4 irAE hepatitis (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) increase)	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 5 irAE	0 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 3 irAE colitis	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 3 irAE hemorrhagic cystitis	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 3 irAE maculopapular rash	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 3 irAE mucositis oral	1 Participants	—
Number of Participants With Clinically Important Immune-related Adverse Events (for the Lead-In Cohort) Grade 4 autoimmune diabetes (hyperglycemia)	1 Participants	—

PRIMARY outcome

Timeframe: From baseline to radical prostatectomy (approximately week 9)

Changes in T-cell infiltration in the tumor after neoadjuvant treatment with PROSTVAC and nivolumab, is defined as difference in density of cytotoxic T lymphocytes (CD8 T) cells and clusters of differentiation 4 (CD4 T) cells infiltrate from baseline to post-treatment (radical prostatectomy performed at week 9), calculated utilizing computer automated staining analysis. The analysis was done per tissue compartment (normal region, intra-tumoral and invasive margin). We hypothesized an increase in T cell infiltration after treatment. Statistically significant changes in T-cell infiltration are those with p\<0.05; to 0.05. The changes are not statistically significant.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the total tissue at baseline	64.02 Cell/mm^2 of tissue Interval 41.2 to 133.7	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the total tissue at prostatectomy at week 9	154.3 Cell/mm^2 of tissue Interval 80.2 to 312.3	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the center of the tumor at baseline	57.9 Cell/mm^2 of tissue Interval 26.5 to 103.8	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the center of the tumor at prostatectomy at week 9	110.5 Cell/mm^2 of tissue Interval 58.3 to 221.0	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the invasive margin at baseline	56.4 Cell/mm^2 of tissue Interval 49.3 to 88.5	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the invasive margin at prostatectomy at week 9	304 Cell/mm^2 of tissue Interval 136.5 to 522.5	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the normal region at baseline	99.15 Cell/mm^2 of tissue Interval 58.2 to 207.8	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD8+ T cell in the normal region at prostatectomy at week 9	124.5 Cell/mm^2 of tissue Interval 80.5 to 231.5	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the total tissue at baseline	114.4 Cell/mm^2 of tissue Interval 61.1 to 184.9	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the total tissue at prostatectomy at week 9	478.8 Cell/mm^2 of tissue Interval 319.3 to 632.1	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the center of the tumor at baseline	109.5 Cell/mm^2 of tissue Interval 70.5 to 149.7	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell in the center of the tumor at prostatectomy at week 9	394.5 Cell/mm^2 of tissue Interval 114.3 to 676.0	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the invasive margin at baseline	161 Cell/mm^2 of tissue Interval 59.8 to 206.4	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the invasive margin at prostatectomy at 9 weeks	672.5 Cell/mm^2 of tissue Interval 587.0 to 1225.3	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the normal region at baseline	57.4 Cell/mm^2 of tissue Interval 37.5 to 113.4	—
Changes in T-cell Infiltration in the Tumor After Neoadjuvant Treatment (Only for the Neoadjuvant Cohort) CD4+ T cell helper in the normal region at prostatectomy at week 9	246.5 Cell/mm^2 of tissue Interval 97.0 to 361.3	—

SECONDARY outcome

Timeframe: From baseline throughout study completion, an average of 20 weeks.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With Clinically Important Immune-related Adverse Events (Only for Neoadjuvant Cohort)	0 Participants	—

SECONDARY outcome

Timeframe: Week 4, week 10, and week 20 after therapy compared to baseline

Changes in soluble immune mediating factors were defined as differences in sCD27 concentration between pre- and post-treatment samples and were measured by enzyme-linked immunosorbent assay (ELISA) and Mesoscale Assay. P values were calculated using the Wilcoxon Signed Rank Test. We hypothesized an increase in sCD27 after treatment. Statistically significant changes in soluble analyzes are those with p\<0.05; to 0.05 means no statistically significant changes.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera sCD27 at baseline	98.6 U/mL Interval 85.6 to 122.5	77.2 U/mL Interval 59.8 to 98.9
Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera sCD27 week 4	127.9 U/mL Interval 85.0 to 164.0	80.2 U/mL Interval 71.4 to 109.5
Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera sCD27 week 10	108.8 U/mL Interval 90.2 to 138.3	82 U/mL Interval 70.1 to 102.8
Changes in Soluble Immune Mediating Factors (Soluble Cluster of Differentiation 27 (sCD27) in Sera SCD27 week 20	131.9 U/mL Interval 95.5 to 141.2	81 U/mL Interval 68.3 to 95.5

SECONDARY outcome

Timeframe: Week 4, week 10, and week 20 after therapy compared to baseline

Changes in soluble immune mediating factors were defined as differences in TNFα, and IL-10 concentration between pre- and post-treatment samples and were measured by enzyme-linked immunosorbent assay (ELISA) and Mesoscale Assay. P values were calculated using the Wilcoxon Signed Rank Test. We hypothesized an increase in TNFα and IL-10 after treatment. Statistically significant changes in soluble analyzes are those with p\<0.05, p0.05 means the changes are not statistically significant.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera TNFα Baseline	2.8 pg/mL Interval 2.5 to 3.9	2.5 pg/mL Interval 1.6 to 3.0
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera TNFα Week 4	3.5 pg/mL Interval 3.1 to 4.9	2.7 pg/mL Interval 2.3 to 4.1
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera TNFα Week 10	3 pg/mL Interval 2.7 to 4.9	2.8 pg/mL Interval 2.4 to 3.2
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera TNFα Week 20	3.4 pg/mL Interval 3.0 to 4.1	2.4 pg/mL Interval 2.1 to 3.1
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera IL-10 Baseline	0.3 pg/mL Interval 0.2 to 0.4	0.3 pg/mL Interval 0.2 to 0.3
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera IL-10 Week 4	0.6 pg/mL Interval 0.4 to 0.8	0.5 pg/mL Interval 0.3 to 0.6
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera IL-10 Week 10	0.5 pg/mL Interval 0.3 to 1.0	0.4 pg/mL Interval 0.3 to 0.6
Changes in Soluble Immune Mediating Factors (Tumor Necrosis Factor Alpha (TNFα) and Interleukin 10 (IL-10) in Sera IL-10 Week 20	0.5 pg/mL Interval 0.4 to 0.9	0.5 pg/mL Interval 0.3 to 0.6

SECONDARY outcome

Timeframe: Baseline (biopsy before first PROSTVAC administration) and at time of radical prostatectomy (on week 9)

Changes in PD-L1 expression is defined as changes in density of cells positive for PDL1 and was analyzed by immunohistochemistry staining using the clone 22C3. Placenta tissue was used as a positive control. Previous studies have shown that high PDL1 expression is associated with poor clinical outcomes in prostate cancer participants. An increase of PDL1 after immunotherapy could indicate a resistance of the tumor to the treatment. Values can go from 0 to 100. 50% of Tumor cells is considered positive for PDL1. The sample will be considered positive if at least 1% or tumor cells express PDL1.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Percent Change of Tumor Cells Expressing Programmed Death-ligand 1 (PDL-1) (for the Neo-adjuvant Cohort) Baseline	0 Percent change in cell/mm^2 of tissue Standard Deviation 0	—
Percent Change of Tumor Cells Expressing Programmed Death-ligand 1 (PDL-1) (for the Neo-adjuvant Cohort) Time of prostatectomy (week 9)	0.07 Percent change in cell/mm^2 of tissue Standard Deviation 0.16	—

SECONDARY outcome

Timeframe: Week 4 and week 10 after therapy compared to baseline.

Peripheral blood samples were collected at baseline and after treatment start via apheresis and cryopreserved peripheral blood mononucleate cells (PBMCs) were analyzed through multicolor flow cytometry to assess cell subsets, i.e. cluster of differentiation 4 (CD4+) T cells, cytotoxic T cells (CD8+) T cells, Tregs, B cells, Natural Killer (NK) cells, NK-T cells, conventional Dendritic Cells (cDCs), plasmocytoid DCs (pDCs), myeloid-derived suppressor cells (MDSCs), and monocytes and refined subsets related to their maturation/function. P values were calculated using the Wilcoxon Signed Rank Test. Statistically significant changes in immune cell subsets are defined as those with p\<0.05 and \>50% of participants having a \>25% change in a given subset.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in Immune Cell Subsets in the Peripheral Blood Treg ICOS+ cells week 4 post treatment	0.7 percentage of PBMC's Interval 0.5 to 0.9	0.5 percentage of PBMC's Interval 0.3 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood Treg ICOS+ cells week 10 post treatment	0.4 percentage of PBMC's Interval 0.2 to 0.6	0.5 percentage of PBMC's Interval 0.3 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood NK ki67+ cells Baseline	0.7 percentage of PBMC's Interval 0.5 to 0.8	0.5 percentage of PBMC's Interval 0.3 to 0.8
Changes in Immune Cell Subsets in the Peripheral Blood NK ki67+ cells week 4 post treatment	1 percentage of PBMC's Interval 0.6 to 1.7	0.5 percentage of PBMC's Interval 0.3 to 0.8
Changes in Immune Cell Subsets in the Peripheral Blood NK NKG2D+ cells Baseline	1 percentage of PBMC's Interval 0.5 to 1.3	1.2 percentage of PBMC's Interval 1.0 to 2.2
Changes in Immune Cell Subsets in the Peripheral Blood NK NKG2D+ cells week 4 post treatment	1.7 percentage of PBMC's Interval 1.0 to 2.0	1.6 percentage of PBMC's Interval 0.8 to 3.1
Changes in Immune Cell Subsets in the Peripheral Blood NK NKp46+ cells Baseline	2.5 percentage of PBMC's Interval 2.1 to 3.0	2 percentage of PBMC's Interval 1.2 to 2.5
Changes in Immune Cell Subsets in the Peripheral Blood NK NKp46+ cells week 4 post treatment	3.3 percentage of PBMC's Interval 2.6 to 4.3	2.4 percentage of PBMC's Interval 1.5 to 2.7
Changes in Immune Cell Subsets in the Peripheral Blood NK NKp46+ cells week 10 post treatment	3.1 percentage of PBMC's Interval 2.2 to 3.5	1.8 percentage of PBMC's Interval 1.1 to 2.7
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ naive T cells week 4 post treatment	2.6 percentage of PBMC's Interval 0.7 to 4.7	1.7 percentage of PBMC's Interval 1.0 to 2.4
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ naive T cells week 10 post treatment	2.3 percentage of PBMC's Interval 0.7 to 4.6	2.1 percentage of PBMC's Interval 1.6 to 2.5
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ CM T cells Baseline	0.3 percentage of PBMC's Interval 0.2 to 0.4	0.4 percentage of PBMC's Interval 0.2 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ CM T cells week 4 post treatment	0.2 percentage of PBMC's Interval 0.1 to 0.3	0.2 percentage of PBMC's Interval 0.1 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ CM T cells week 10 post treatment	0.2 percentage of PBMC's Interval 0.1 to 0.3	0.4 percentage of PBMC's Interval 0.3 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood gMDSC Baseline	0 percentage of PBMC's Interval 0.0 to 0.1	0 percentage of PBMC's Interval 0.0 to 0.1
Changes in Immune Cell Subsets in the Peripheral Blood Intermediate monocytes Baseline	0.2 percentage of PBMC's Interval 0.1 to 0.7	0.4 percentage of PBMC's Interval 0.3 to 0.7
Changes in Immune Cell Subsets in the Peripheral Blood Intermediate monocytes week 10 post treatment	0.2 percentage of PBMC's Interval 0.2 to 0.6	0.5 percentage of PBMC's Interval 0.3 to 0.7
Changes in Immune Cell Subsets in the Peripheral Blood Non-classical monocytes Baseline	0.7 percentage of PBMC's Interval 0.2 to 1.3	0.8 percentage of PBMC's Interval 0.5 to 1.2
Changes in Immune Cell Subsets in the Peripheral Blood Non-classical monocytes week 4 post treatment	0.9 percentage of PBMC's Interval 0.2 to 1.6	1.6 percentage of PBMC's Interval 0.9 to 3.0
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ CM T cells week 4 post treatment	7.5 percentage of PBMC's Interval 4.7 to 10.8	5.9 percentage of PBMC's Interval 4.4 to 8.6
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ naive T cells Baseline	9 percentage of PBMC's Interval 3.6 to 13.9	6.7 percentage of PBMC's Interval 4.7 to 9.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ naive T cells week 10 post treatment	8.8 percentage of PBMC's Interval 3.3 to 14.8	5.7 percentage of PBMC's Interval 3.9 to 12.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ T cells Baseline	33.4 percentage of PBMC's Interval 24.5 to 42.9	27 percentage of PBMC's Interval 21.9 to 35.7
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ T cells week 4 post treatment	27.2 percentage of PBMC's Interval 24.0 to 41.5	20.3 percentage of PBMC's Interval 16.4 to 29.0
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ T cells week 10 post treatment	24.5 percentage of PBMC's Interval 20.5 to 38.0	25.4 percentage of PBMC's Interval 23.6 to 36.1
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ T cells Baseline	11.7 percentage of PBMC's Interval 8.4 to 22.1	10.4 percentage of PBMC's Interval 9.2 to 14.1
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ T cells week 4 post treatment	11 percentage of PBMC's Interval 9.5 to 19.0	9.4 percentage of PBMC's Interval 7.0 to 16.0
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ T cells week 10 post treatment	10.6 percentage of PBMC's Interval 7.9 to 20.4	10.8 percentage of PBMC's Interval 9.8 to 12.6
Changes in Immune Cell Subsets in the Peripheral Blood Treg cells Baseline	0.9 percentage of PBMC's Interval 0.6 to 1.0	0.9 percentage of PBMC's Interval 0.8 to 1.1
Changes in Immune Cell Subsets in the Peripheral Blood Treg cells week 4 post treatment	1.1 percentage of PBMC's Interval 0.9 to 1.4	1 percentage of PBMC's Interval 0.7 to 1.1
Changes in Immune Cell Subsets in the Peripheral Blood Treg cells week 10 post treatment	0.6 percentage of PBMC's Interval 0.4 to 1.1	0.9 percentage of PBMC's Interval 0.7 to 1.3
Changes in Immune Cell Subsets in the Peripheral Blood cDC cells Baseline	0.2 percentage of PBMC's Interval 0.1 to 0.4	0.5 percentage of PBMC's Interval 0.3 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood cDC cells week 4 post treatment	0.2 percentage of PBMC's Interval 0.1 to 0.3	0.4 percentage of PBMC's Interval 0.3 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood cDC cells week 10 post treatment	0.2 percentage of PBMC's Interval 0.1 to 0.3	0.3 percentage of PBMC's Interval 0.2 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood Monocytes Baseline	6.8 percentage of PBMC's Interval 3.0 to 13.4	12.5 percentage of PBMC's Interval 7.7 to 18.0
Changes in Immune Cell Subsets in the Peripheral Blood Monocytes week 4 post treatment	7.5 percentage of PBMC's Interval 3.7 to 11.3	14.6 percentage of PBMC's Interval 9.6 to 22.4
Changes in Immune Cell Subsets in the Peripheral Blood Monocytes week 10 post treatment	6.2 percentage of PBMC's Interval 3.8 to 15.9	10.9 percentage of PBMC's Interval 6.1 to 15.2
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ki67+ T cells Baseline	0.9 percentage of PBMC's Interval 0.7 to 1.0	0.5 percentage of PBMC's Interval 0.4 to 0.7
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ki67+ T cells week 4 post treatment	1.3 percentage of PBMC's Interval 1.0 to 1.9	0.6 percentage of PBMC's Interval 0.5 to 1.0
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ki67+ T cells week 10 post treatment	0.9 percentage of PBMC's Interval 0.7 to 1.2	0.6 percentage of PBMC's Interval 0.5 to 0.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+EM ki67+ T cells Baseline	0.6 percentage of PBMC's Interval 0.4 to 0.7	0.4 percentage of PBMC's Interval 0.3 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood CD4+EM ki67+ T cells week 4 post treatment	0.8 percentage of PBMC's Interval 0.7 to 1.3	0.5 percentage of PBMC's Interval 0.4 to 0.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+EM ki67+ T cells week 10 post treatment	0.7 percentage of PBMC's Interval 0.5 to 0.9	0.5 percentage of PBMC's Interval 0.4 to 0.6
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ ICOS+ T cells Baseline	2.6 percentage of PBMC's Interval 2.0 to 4.0	2 percentage of PBMC's Interval 1.6 to 2.5
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ ICOS+ T cells week 4 post treatment	3.8 percentage of PBMC's Interval 2.8 to 5.3	2.3 percentage of PBMC's Interval 1.8 to 3.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ ICOS+ T cells week 10 post treatment	2.2 percentage of PBMC's Interval 1.7 to 2.9	2.3 percentage of PBMC's Interval 1.9 to 3.1
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ ki67+ T cells Baseline	0.2 percentage of PBMC's Interval 0.2 to 0.3	0.2 percentage of PBMC's Interval 0.1 to 0.3
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ ki67+ T cells week 4 post treatment	0.5 percentage of PBMC's Interval 0.3 to 0.9	0.2 percentage of PBMC's Interval 0.2 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ ki67+ T cells week 10 post treatment	0.3 percentage of PBMC's Interval 0.2 to 0.4	0.3 percentage of PBMC's Interval 0.2 to 0.3
Changes in Immune Cell Subsets in the Peripheral Blood Treg ICOS+ cells Baseline	0.5 percentage of PBMC's Interval 0.4 to 0.6	0.4 percentage of PBMC's Interval 0.3 to 0.5
Changes in Immune Cell Subsets in the Peripheral Blood NK ki67+ cells week 10 post treatment	0.8 percentage of PBMC's Interval 0.4 to 1.1	0.4 percentage of PBMC's Interval 0.3 to 0.7
Changes in Immune Cell Subsets in the Peripheral Blood NK NKG2D+ cells week 10 post treatment	1.2 percentage of PBMC's Interval 0.6 to 1.8	2.3 percentage of PBMC's Interval 1.0 to 3.2
Changes in Immune Cell Subsets in the Peripheral Blood CD8+ naive T cells Baseline	3.3 percentage of PBMC's Interval 0.7 to 4.8	2.2 percentage of PBMC's Interval 1.5 to 2.8
Changes in Immune Cell Subsets in the Peripheral Blood Non-classical monocytes week 10 post treatment	0.4 percentage of PBMC's Interval 0.3 to 1.2	0.9 percentage of PBMC's Interval 0.6 to 1.5
Changes in Immune Cell Subsets in the Peripheral Blood gMDSC week 4 post treatment	0 percentage of PBMC's Interval 0.0 to 0.1	0.2 percentage of PBMC's Interval 0.0 to 0.2
Changes in Immune Cell Subsets in the Peripheral Blood gMDSC week 10 post treatment	0 percentage of PBMC's Interval 0.0 to 0.1	0.1 percentage of PBMC's Interval 0.0 to 0.2
Changes in Immune Cell Subsets in the Peripheral Blood Intermediate monocytes week 4 post treatment	0.4 percentage of PBMC's Interval 0.1 to 0.8	0.7 percentage of PBMC's Interval 0.5 to 1.8
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ CM T cells Baseline	10 percentage of PBMC's Interval 7.3 to 13.6	9.3 percentage of PBMC's Interval 6.7 to 11.2
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ CM T cells week 10 post treatment	7.6 percentage of PBMC's Interval 3.3 to 9.5	9 percentage of PBMC's Interval 7.1 to 9.9
Changes in Immune Cell Subsets in the Peripheral Blood CD4+ naive T cells week 4 post treatment	8.5 percentage of PBMC's Interval 3.9 to 16.6	4.7 percentage of PBMC's Interval 3.5 to 7.4

SECONDARY outcome

Timeframe: At baseline and at week 9

Population: This analysis was not performed because the technology developed by Epic Sciences was still in development, thus samples were not sent to the off-site center to perform analysis.

Blood samples will be collected at baseline and after treatment, and aliquoted onto slides and examined, cytokeratin-positive/lymphocyte common antigen (CD45)-negative cells with an intact nucleus and a malignancy-consistent morphology will be identified as CTCs, and their exact positions on the slides recorded.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline and time of radical prostatectomy (average of week 9)

Complete pathologic response is defined as the absence of detectable malignant cells in the prostatectomy specimen evaluated by standard histologic techniques.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With a Pathologic Complete Response (pCR) (Only for Neoadjuvant Cohort)	0 Participants	—

SECONDARY outcome

Timeframe: From baseline throughout study completion, an average of 1.4 years.

Best serologic response secondary to immune treatment was reported. Change in Prostate-specific Antigen (PSA) was used to identify serological responses among participants in the lead-in cohort. Complete Serological Response was defined as PSA level less than 0.2 ng/mL measured for 2 consecutive measurements at least 4 weeks apart. Partial Serological Response was defined as decline of PSA at least 50% measured for 2 consecutive measurements at least 4 weeks apart. Serological Progression: Serological progression will only be measured once PSA has risen above 4 ng/mL and this value must be 50% above the PSA level before commencing treatment. Increase in PSA more than 50% of nadir (lowest PSA on treatment). Values must be measured for 2 consecutive measurements at least 2 weeks apart. The date of the first increase will be recorded as progression. Stable disease: not meeting progressive disease (PD) criteria for ≥12 weeks from treatment start.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With Serologic Response Complete Serological Response	1 Participants	—
Number of Participants With Serologic Response Serological Progressive Disease	4 Participants	—
Number of Participants With Serologic Response Partial Serological Response	1 Participants	—
Number of Participants With Serologic Response Serological Stable Disease	6 Participants	—

SECONDARY outcome

Timeframe: From time of prostatectomy through study completion, an average of 10 weeks

Biochemical recurrence following radical prostatectomy is defined as at least two prostate-specific antigen (PSA) values that are 0.2 ng/mL or higher.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Rate of Biochemical Recurrence After Prostatectomy (Only for Neoadjuvant Cohort)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From baseline to closest date to prostatectomy, average on week 9.

Population: 4/12 participants were not analyzed because MRI was not performed due to logistical issues.

MRI of the prostate was performed to assess for changes in imaging characteristics of prostate cancer pre and post vaccination. MRI changes secondary to immune treatment is defined as increase or decrease in the size of lesions from baseline (pre-vaccine) measurements. Decrease from baseline to after treatment would represent a positive outcome.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=8 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in Magnetic Resonance Imaging (MRI) Secondary to Immune Treatment (Only for Neoadjuvant Cohort) Mean largest lesion measurement at baseline	16.5 mm Interval 8.0 to 24.0	—
Changes in Magnetic Resonance Imaging (MRI) Secondary to Immune Treatment (Only for Neoadjuvant Cohort) Mean targeted lesion measurement after treatment	17.3 mm Interval 9.0 to 25.0	—

SECONDARY outcome

Timeframe: From baseline to closest date to prostatectomy, average on week 9.

Population: 4/12 participants were not analyzed because MRI was not performed due to logistical issues.

Apparent diffusion coefficient (ADC) mapping in magnetic resonance imaging (MRI) is an indicator of tumor cell density. This outcome aims to capture any changes in ADC within the prostate tissue before and after the treatment administration. ADC changes secondary to immune treatment are defined as increase or decrease in ADC from baseline (pre-treatment) measurements. Low ADC values in tumors reflect areas of cell proliferation, and high ADC values reflects necrotic and acellular areas.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=8 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Changes in Apparent Diffusion Coefficient (ADC) Mapping, Secondary to Immune Treatment (Only for Neoadjuvant Cohort) Mean ADC value for all measurable lesions at baseline	1220.6 10^6 mm^2/s Standard Deviation 218.4	—
Changes in Apparent Diffusion Coefficient (ADC) Mapping, Secondary to Immune Treatment (Only for Neoadjuvant Cohort) Mean ADC value for all measurable lesions after treatment	1236.1 10^6 mm^2/s Standard Deviation 244.6	—

SECONDARY outcome

Timeframe: Baseline and at time of prostatectomy (approximately week 9)

Intraprostatic Treg cell infiltration was measured by computer automated staining analysis pre and post treatment. Quantification will be reported as number of stained cells per mm\^2 of tissue.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the invasive margin at prostatectomy	3.5 Cell/mm^2 of tissue Interval 0.0 to 9.75	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the total tissue at baseline	0.3 Cell/mm^2 of tissue Interval 0.0 to 2.7	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the total tissue at prostatectomy	1.3 Cell/mm^2 of tissue Interval 0.0 to 5.3	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the center of the tumor at baseline	0 Cell/mm^2 of tissue Interval 0.0 to 2.5	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the center of the tumor at prostatectomy	1.5 Cell/mm^2 of tissue Interval 0.0 to 5.25	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the invasive margin at baseline	0 Cell/mm^2 of tissue Interval 0.0 to 0.3	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the normal region at baseline	0 Cell/mm^2 of tissue Interval 0.0 to 0.0	—
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4+) and Forkhead Box P3 (FOX-P3) Staining (Only for Neoadjuvant Cohort) T regs in the normal region at prostatectomy	0 Cell/mm^2 of tissue Interval 0.0 to 4.25	—

SECONDARY outcome

Timeframe: Weeks 7-10 and 17-22 compared to baseline

Population: 1/12 were not analyzed in the lead-in cohort because there was an insufficient number of viable peripheral blood mononuclear cells (PBMC) to perform the analysis.

The number of participants who developed positive PSA-Specific T cell responses secondary to immune treatment will be reported. Peripheral prostatic specific antigen (PSA)-specific T cells at baseline and after therapy were assessed. PSA-specific T cells were those producing cytokine (Interferon gamma (IFNγ), Tumor Necrosis Factor Alpha (TNFα), Interleukin-2 (IL-2) or positive for the degranulation marker cluster of differentiation 107a (CD107a) following in vitro stimulation with PSA-15-mer peptides compared to a negative control peptide pool, measured by intracellular cytokine staining. A positive response will be defined as a \>2-fold increase in PSA-specific T cells after therapy compared to baseline.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=11 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With Peripheral Prostate-Specific Antigen (PSA)-Specific T Secondary To Immune Treatment Participants with PSA-specific T cells at baseline	2 Participants	6 Participants
Number of Participants With Peripheral Prostate-Specific Antigen (PSA)-Specific T Secondary To Immune Treatment Participants with positive PSA-specific Tcell response 7-10weeks post treatment compared to baseline	7 Participants	3 Participants
Number of Participants With Peripheral Prostate-Specific Antigen (PSA)-Specific T Secondary To Immune Treatment Participants with positive PSAspecific Tcell response 17-22weeks post treatment compared to baseline	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline throughout study completion (average 1.4 years)

Population: 7/12 participants had measurable disease at baseline and were analyzed for this outcome.

The best overall response is the best response recorded from the start of the treatment until disease progression/ recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=7 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Best Overall Response for Participants With Measurable Disease (Only in the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort) Complete Response	2 Participants	—
Best Overall Response for Participants With Measurable Disease (Only in the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort) Partial Response	0 Participants	—
Best Overall Response for Participants With Measurable Disease (Only in the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort) Stable Disease	3 Participants	—
Best Overall Response for Participants With Measurable Disease (Only in the Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort) Progressive Disease	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First study intervention, Study Day 1, to 30 days after participant received last study drug administration. Approximately 1.4 years for the metastatic castration-resistant prostate cancer cohort, and an average of 20 weeks for the neoadjuvant cohort.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-F on week 2, 4, and 8. Nivolumab will be administered on week 2, 4, 6, 8 and 10. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo restaging scans on week 12. If no progressive disease (PD), option to continue treatment with nivolumab every 2 weeks and PROSTVAC-F every 4 weeks until intolerance or progression. Option to extend nivolumab interval to 4 weeks for participants who remain on protocol beyond 1 year. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.	Neoadjuvant Cohort n=12 Participants Prostate-specific antigen (PSA)-TRICOM vaccinia (PROSTVAC)-V on week 0 followed by booster injection called PROSTVAC-fowlpox (F) on 2, 4 and 8 weeks. Nivolumab will be administered on week 2, 4, and 8. When administered on the same day, the preferred order of administration is PROSTVAC first followed by nivolumab. Participants will undergo prostatectomy on week 9. PROSTVAC-V/F: PROSTVAC-V (vaccinia) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 2x10\^8 infectious units. PROSTVAC-F (fowlpox) will be administered subcutaneously in an extremity (e.g., thigh) at a dose of 1x10\^9 infectious units. Nivolumab: Nivolumab is to be administered as a flat dose over approximately 30-minutes via intravenous (IV) infusion.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	12 Participants	12 Participants

Adverse Events

Lead-in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Cohort

Serious events: 6 serious events

Other events: 12 other events

Deaths: 0 deaths

Neoadjuvant Cohort

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. James L. Gulley

National Cancer Institute

Phone: 301-480-716

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place