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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

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 is a plasmid DNA, produced in E. coli, that encodes the complementary deoxyribonucleic acid (cDNA) for human prostatic acid phosphatase (PAP).

pTVG-HP

pTVG-AR

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

Douglas McNeel, MD, PhD

This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer. The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the percentage of patients experiencing objective anti-tumor effect as measured by PSA declines and/or objective radiographic responses. Participants must be 18 years of age or older and can expect to be on treatment for 2 years (32 cycles) and on study for up to 4 years (including 2 years of follow up via phone).

1:1 randomized, open-label, multi-institution phase II trial

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

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

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.

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

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.

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.

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.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer	NCT04090528	Castration-resi... Metastatic Canc... Prostate Cancer	pTVG-HP pTVG-AR Pembrolizumab	18 Years -	University of Wisconsin, Madison
pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer	NCT04090528	Castration-resi... Metastatic Canc... Prostate Cancer	pTVG-HP pTVG-AR Pembrolizumab	18 Years -	University of Wisconsin, Madison

Spots Global Cancer Trial Database for prostatic acid phosphatase