NCT03007732

Pembrolizumab +/- SD-101 in Hormone-Naïve Oligometastatic Prostate Cancer With RT and iADT

Phase 2 Trial Pembrolizumab or Pembrolizumab in Combination With Intratumoral SD-101 Therapy in Patients With Hormone-Naïve Oligometastatic Prostate Cancer Receiving Stereotactic Body Radiation Therapy and Intermittent Androgen Deprivation Therapy

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: David Oh · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a non-comparative open-label multicenter Phase 2 clinical trial combining stereotactic body radiation therapy (SBRT) and pembrolizumab with or without intratumoral SD-101 in participants with newly diagnosed hormone-naive oligometastatic prostate cancer.

Detailed description

This randomized phase II trial studies how well androgen deprivation therapy, pembrolizumab, and stereotactic body radiation therapy with or without toll-like receptor 9 (TLR9) agonist SD-101 in treating participants with prostate cancer and cancer in all oligometastatic sites that has spread to other places in the body. Androgen can cause the growth of tumor cells. Androgen deprivation therapy, such as leuprolide acetate, prednisone, and abiraterone acetate may lessen the amount of androgen made by the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Colony-stimulating factors, such as TLR9 agonist SD-101, may increase the production of blood cells. It is not yet known whether giving androgen deprivation therapy, pembrolizumab, and stereotactic body radiation therapy with or without TLR9 agonist SD-101 may work better in treating participants with prostate cancer and cancer in all oligometastatic sites. PRIMARY OBJECTIVES COHORT 1: \-- To assess the safety associated with giving RT and pembrolizumab with or without intratumoral SD-101. COHORT 2: * To continue to assess the safety associated with giving RT and pembrolizumab with or without intratumoral SD-101. * To assess if the rate of PSA \< nadir + 2 ng/mL at 15 months in participants with non-castrate levels of testosterone is greater than the historical control in each study arm. SECONDARY OBJECTIVES COHORT 2 ONLY: * To determine the rate of testosterone-prostate specific antigen (PSA) uncoupling in each study arm in Cohort 2. Testosterone-PSA uncoupling is defined as PSA \< 50% baseline and \< 20ng/mL for at least 3 months after testosterone recovers to \>150 ng/dL. In participants with metastatic hormone sensitive prostate cancer off hormonal therapy, \>90% of participants are expected to have PSA increase to \> 50% baseline after 3 months of testosterone recovery. * To estimate time to clinical progression in each study arm in Cohort 2. * To estimate progression-free survival (PFS) in each study arm Cohort 2. EXPLORATORY OBJECTIVE * To assess peripheral and tumor-based biomarkers of response and resistance in both cohorts. * To define the treatment-induced effects on circulating immune cells in both cohorts. * To explore remodeling of circulating T cell repertoire in both cohorts. * To explore the concordance of Prostate-Specific Membrane Antigen (PSMA) - Positron Emission Tomography (PET) scanning with conventional imaging in oligometastatic prostate cancer participants in both cohorts.

Conditions

• Prostatic Neoplasms

Interventions

Type	Name	Description
DRUG	Pembrolizumab	200 mg IV every 21 days for up to 13 doses (Arms 1 and 2)
DRUG	SD-101	5 mg will be delivered to the dominant prostatic tumor lesion at time of fiducial marker placement (1-5 weeks prior to Cycle 1, Day 1) and and 1-3 weeks after Cycle 1 Day 1
DRUG	Leuprolide acetate	22.5 mg will be given intramuscularly (IM). First injection 3 months prior to Cycle 1 Day 1. Intermittent androgen deprivation therapy will be given every 3 months starting Cycle 1, Day 1 for 3 additional doses.
DRUG	Abiraterone Acetate	1000 mg oral dosage will be given daily for 3 months prior to Cycle 1, Day 1 and daily for 9 months starting Cycle 1, Day 1.
DRUG	Prednisone	5 mg oral dosage will be given daily for 3 months prior to Cycle 1 Day 1 and daily for 9 months starting Cycle 1, Day 1.
RADIATION	Stereotactic Body Radiation Therapy	7 Gy x 5 fractions (35 Gy total) 1-2 weeks after fiducial marker placement and simulation over 10-14 days.

Timeline

• Start date: 2017-05-17
• Primary completion: 2025-03-31
• Completion: 2025-03-31
• First posted: 2017-01-02
• Last updated: 2025-12-05
• Results posted: 2025-12-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study