Trial Outcomes & Findings for pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer (NCT NCT04090528)

Last Updated: 2025-12-05

Results Overview

The expected 6-months PFS rate in Arm 1 (pTVG-HP DNA vaccine and Pembrolizumab) in this participant population is 20-30%. It is hypothesized that adding pTVG-AR DNA vaccine (Arm 2) will increase the 6-months PFS rate to at least 55%. The 6-month PFS rate will be calculated for each study arm along with the corresponding two-sided 95% confidence interval which will be constructed using the Wilson score method. Participants who withdraw from the study without a progression or death event before the 6-month assessment will be excluded from this analysis. The stratified (by randomization strata) Mantel-Haenszel test will be used to compare the 6-months PFS rates between study arms.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

6 months

Results posted on

2025-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: One DNA Vaccine 100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles pTVG-HP: pTVG-HP is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP). Pembrolizumab: Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.	Arm 2: Two DNA Vaccines 100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4 pTVG-HP: pTVG-HP is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP). pTVG-AR: pTVG-AR is a plasmid DNA Pembrolizumab: Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.
Overall Study STARTED	30	30
Overall Study Analysis Population	30	30
Overall Study COMPLETED	21	17
Overall Study NOT COMPLETED	9	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: One DNA Vaccine 100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles pTVG-HP: pTVG-HP is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP). Pembrolizumab: Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.	Arm 2: Two DNA Vaccines 100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4 pTVG-HP: pTVG-HP is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP). pTVG-AR: pTVG-AR is a plasmid DNA Pembrolizumab: Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of patients with multiple different types of cancer.
Overall Study participants still on study	9	13

Baseline Characteristics

pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: One DNA Vaccine n=30 Participants 100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles	Arm 2: Two DNA Vaccines n=30 Participants 100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4	Total n=60 Participants Total of all reporting groups
Age, Continuous	70.0 years STANDARD_DEVIATION 9.5 • n=37 Participants	72.4 years STANDARD_DEVIATION 7.0 • n=37 Participants	71.2 years STANDARD_DEVIATION 8.4 • n=74 Participants
Sex: Female, Male Female	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Sex: Female, Male Male	30 Participants n=37 Participants	30 Participants n=37 Participants	60 Participants n=74 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=37 Participants	30 Participants n=37 Participants	60 Participants n=74 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Race (NIH/OMB) Black or African American	3 Participants n=37 Participants	2 Participants n=37 Participants	5 Participants n=74 Participants
Race (NIH/OMB) White	27 Participants n=37 Participants	28 Participants n=37 Participants	55 Participants n=74 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants	0 Participants n=37 Participants	0 Participants n=74 Participants
Region of Enrollment United States	30 participants n=37 Participants	30 participants n=37 Participants	60 participants n=74 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Arm 1: One DNA Vaccine n=30 Participants 100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles	Arm 2: Two DNA Vaccines n=30 Participants 100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4
Progression-Free Survival (PFS)	51 percentage of participants Interval 30.0 to 69.0	45 percentage of participants Interval 22.0 to 66.0

SECONDARY outcome

Timeframe: up to 2 years

The number of responses will be summarized in tabular format, stratified by study arm. Of note, objective response rate using radiographic criteria will apply only to subjects with RECIST measurable disease (i.e. not subjects with bone-only metastatic disease). Response rates will be calculated for each study arm along with the corresponding two-sided 95% confidence interval which will be constructed using the Wilson score method. The stratified (by randomization strata) Mantel-Haenszel test will be used to compare the overall objective response rates between study arms

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 2 years

The number of responses will be summarized in tabular format, stratified by study arm. PSA Response Rates will be calculated for each study arm along with the corresponding two-sided 95% confidence interval which will be constructed using the Wilson score method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Progression-Free Survival will be analyzed using the Kaplan-Meier method. Median PFS will be calculated for each study arm and reported along with the corresponding 95% confidence intervals will which will constructed using the nonparametric Brookmeyer and Crowley method. The stratified (by randomization strata) log-rank test will be used to compare PFS between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Duration of PSA and objective response will be analyzed using the Kaplan-Maier method. The median duration of PSA and objective response will be calculated and report along with the corresponding 95% confidence interval which will be constructed using the nonparametric Brookmeyer-Crowley method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Overall Survival will be analyzed using the Kaplan-Meier method. OS will be calculated for each study arm and reported along with the corresponding 95% confidence intervals will which will constructed using the nonparametric Brookmeyer and Crowley method. The stratified (by randomization strata) log-rank test will be used to compare OS between study arms.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

The number and frequencies of antigen-specific Th1 immune responses will be summarized in tabular format for each study arm and both study arms combined. A generalized linear model with a logit link function will be used to evaluate whether antigen-specific Th1 immunity elicited with treatment to either antigen (PAP or AR) is associated with PSA response. The interaction term between treatment arm and antigen-specific Th1 immune will be included in this model.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Participants will be evaluated at each visit by a review of systems based on the most recent version of the NCI common toxicity criteria. Toxicities will be summarized by type and severity in tabular format. 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. Fisher's exact test wi be used to compare toxicity rates between study arms.

Outcome measures

Outcome data not reported

Adverse Events

Arm 1: One DNA Vaccine

Serious events: 4 serious events

Other events: 22 other events

Deaths: 19 deaths

Arm 2: Two DNA Vaccines

Serious events: 4 serious events

Other events: 22 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1: One DNA Vaccine n=30 participants at risk 100 µg pTVG-HP administered intradermally (i.d.) days 1, 8 plus 200 mg Pembrolizumab, administered intravenously on day 1 of 21-day cycles (for 8 cycles) Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 of 21-day cycles x 4 cycles	Arm 2: Two DNA Vaccines n=30 participants at risk 100 µg pTVG-AR administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 1, 2, 5, and 6 alternating with 100 µg pTVG-HP administered intradermally (i.d.) on days 1, 8 plus 200 mg Pembrolizumab administered intravenously day 1 of 21-day cycles, for cycles 3, 4, 7, and 8. Following cycle 8, subsequent 21-days cycles: Pembrolizumab 200 mg IV day 1 of 21-day cycles In the event of PSA rise (25% increase over cycle 9 day 1, minimum of 2 ng/ml), and no evidence of radiographic progression, participants will receive 4 additional vaccine booster cycles: 100 µg pTVG-AR i.d days 1, 8 + 200 mg pembrolizumab IV day 1 of q 21-day cycles, for cycles 1 and 2 followed by 100 µg pTVG-HP i.d. days 1, 8 + 200 mg pembrolizumab IV day 1 in 21-day cycles, for cycles 3 and 4
Endocrine disorders Adrenal insufficiency	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
General disorders Fever	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Nervous system disorders Transient ischemic attack	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Gastrointestinal disorders Nausea	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Investigations Alanine aminotransferase increased	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Investigations Aspartate aminotransferase increased	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Nervous system disorders Cord Compression Event	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.	3.3% 1/30 • participants will be followed for up to 5 years All adverse events (including grade 1 events) with a frequency greater than 5 percent, and any adverse events with grade greater than grade 1, that were believed to be at least possibly related to treatment, are shown for patients treated in Arms 1 and 2. The numbers represent the number of patients experiencing a particular event at any point during the treatment period.

Other adverse events

Additional Information

Douglas G. McNeel, MD PhD

University of Wisconsin - Madison

Phone: (608) 263-4198

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place