Patients receive pTVG-HP plasmid DNA vaccine ID every other week on days 1, 15, 29, 43, 57, and 71 and pembrolizumab IV over 30 minutes every 3 weeks on days 1, 22, 43, and 64.

Patients receive pTVG-HP plasmid DNA vaccine ID as in Arm I and pembrolizumab IV over 30 minutes every 3 weeks on days 85, 106, 127, and 148.

pTVG-HP (100 μg) with rhGM-CSF (208 μg) administered intradermally (i.d.) every 3 weeks, for a maximum of 16 doses. Pembrolizumab 2 mg/kg, with a maximum dose of 200 mg, administered intravenously every 3 weeks, for a maximum of 16 doses, beginning on day 1 after the first pTVG-HP vaccination.

pTVG-HP (100 µg) with rhGM-CSF (208 µg) administered intradermally (i.d.) every 2 weeks, for a maximum of 24 doses Pembrolizumab 2 mg/kg, with a maximum dose of 200 mg, administered intravenously every 4 weeks, for a maximum of 12 doses, beginning on day 1 after the first pTVG-HP vaccination

Hormone-Resistant Prostate Cancer

Metastatic Malignant Neoplasm in the Bone

Metastatic Malignant Neoplasm in the Soft Tissues

Metastatic Prostate Carcinoma

Prostate Adenocarcinoma

Recurrent Prostate Carcinoma

Stage IV Prostate Cancer

Pembrolizumab

pTVG-HP Plasmid DNA Vaccine

Clinical Trials at the University of Wisconsin Carbone Cancer Center

University of Wisconsin Carbone Cancer Center

Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

Pilot Trial of pTVG-HP DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer

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 will be used to compare toxicity rates between study arms.

Serum chemistry and amylase parameters will be summarized using standard descriptive statistics. Changes from the baseline assessment will be evaluated using a paired t-test.

6-month progression-free survival rate, along with corresponding two-sided 95% confidence intervals, will be reported for each arm, and for overall combined study. Wilson score method will be used to construct the confidence intervals. Fisher's exact test will be used to compare 6-month progression-free survival rates between study arms. In order to evaluate the 6-month progression-free rate as a function of baseline time point (pretreatment or 3-months post treatment, analysis will be conducted using two different baseline values: date of randomization, and 3-months disease assessment.

Median time to radiographic progression will be estimated for each, and for both study arms combined, using Kaplan-Meier method. Log-rank test will be used to perform comparison of time to radiographic progression between study arms. A one-sided 0.10 significance level will be used to conduct the comparison of the 6-month progression-free survival rate and time to radiographic progression between study arms. In order to evaluate the median time to radiographic progression as a function of baseline time point (pretreatment or 3-months post treatment), analysis will be conducted.

Will be calculated for each study arm and for both arms combined along with the corresponding 95% confidence intervals. The Wilson score method will be used to construct the confidence intervals. Fisher's exact test will be used to compare the objective response and PSA response rates between study arms. Duration of response will be analyzed using the Kaplan-Meier method.

Number and frequencies of PAP-specific immune responses will be summarized in tabular format for each study arm and both study arms combined. A log-linear model will be used to evaluate whether PAP-specific immune response predicts 6-months progression-free survival rate. Interaction between treatment (pembrolizumab administered sequentially versus delayed) and PAP-specific immune response will be included in the model. Analogously, a Cox proportional hazard regression model will be used to examine the association between PAP-specific immune response and time to radiographic progression.

Number and frequencies of PAP-specific T-cell responses will be summarized in tabular format. Fisher's exact test will be used to compare the PAP-specific T-cell response rates between study arms.

PD-1 and PD-L1 expression levels will be summarized in terms of means, standard deviations and ranges for each study arm separately and for both arms combined. A linear regression model or a negative binomial regression model will be utilized to evaluate effects of schedule (concurrent versus delayed administration pembrolizumab) on PD-1 expression on number of circulating T cells, and PD-L1 expression on number of circulating epithelial cells. Choice of the model will be dependent on distribution of outcome variables (number of circulating T-cells and number of circulating epithelial cells).

University of Wisconsin, Madison

Prostate Cancer Foundation

Madison Vaccines, Inc

Once at least 12 subjects per arm are accrued to Arms 1 and 2, and Arm 3 is open to accrual, accrual will occur only to Arm 3 (other arms will be closed). Extended treatment Arm 4 will open only when Arm 3 has met accrual.

hepatitis a/phosphatase

Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

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