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

NCT03007732 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16703NCI-2017-01340
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (2)

• Change Rate of Prostate-specific Antigen (PSA) < Nadir + 2 ng/mL From First Day of Treatment to 15 Months (Cohort 2)

  Only participants in cohort 2, who achieve testosterone recovery to non-castrate levels (\>150 ng/dL) at 15 months, will be analyzed for the primary endpoint. The rate of PSA \< nadir + 2 ng/mL at 15 months from the start of radiotherapy and cycle 1, day 1 of pembrolizumab, among participants whose testosterone recovers to non-castrate levels (\>150 ng/dL). The point estimate of the rate of PSA \< nadir + 2 ng/mL will be obtained with its 95% confidence interval for participants by arm in cohort 2. All participants who receive any part of a dose of RT, SD-101 or pembrolizumab will be analyzed for efficacy.

  Start of treatment and 15 months (approx. 15 months total)

• Number of Participants With Treatment-related Adverse Events

  Adverse events occurring on study will be summarized for all participants that received study intervention (including pembrolizumab, SD-101, SBRT to prostate, SBRT to oligometastatic sites) by maximum toxicity grade across study arms.

  Up to 15 months

Secondary Outcomes (3)

• Rate of Testosterone-PSA Uncoupling (Cohort 2)

  Up to 15 months

• Median Time to Clinical Progression (Cohort 2)

  Up to 3 years

• Median Progression-free Survival (PFS) (Cohort 2)

  Up to 3 years

Study Arms (4)

Cohort 1, Arm 1: Prostate Only Sites (ADT, SBRT, Pembrolizumab)

EXPERIMENTAL

Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement.

Cohort 1, Arm 2: Prostate Only Sites (ADT, SBRT, Pembrolizumab, SD-101)

EXPERIMENTAL

Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. TLR9 agonist SD-101: Injected into the dominant prostatic tumor lesion at time of fiducial marker placement (1-5weeks prior to Cycle 1 Day 1) and 1-3 weeks after Cycle 1 Day 1 Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement.

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab)

EXPERIMENTAL

Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland and oligometastatic sites via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement.

Drug: Pembrolizumab; Drug: Leuprolide acetate; Drug: Abiraterone Acetate; Drug: Prednisone; Radiation: Stereotactic Body Radiation Therapy

Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

EXPERIMENTAL

Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses (or another FDA approved gonadotropin-releasing hormone agent for 9 months) + abiraterone by mouth daily with prednisone by mouth daily (or equivalent medication per local standard practice) for 9 months starting on Day 1. TLR9 agonist SD-101: Injected into the dominant prostatic tumor lesion at time of fiducial marker placement (1-5weeks prior to Cycle 1 Day 1) and 1-3 weeks after Cycle 1 Day 1 Pembrolizumab: Given IV every 21 days for up to 13 doses Radiotherapy: Given every other day over 10-14 days delivered to the whole prostate gland and oligometastatic sites via stereotactic body radiation therapy (SBRT) starting 1-2 weeks after marker placement.

Drug: Pembrolizumab; Drug: SD-101; Drug: Leuprolide acetate; Drug: Abiraterone Acetate; Drug: Prednisone; Radiation: Stereotactic Body Radiation Therapy

Interventions

Pembrolizumab DRUG

200 mg IV every 21 days for up to 13 doses (Arms 1 and 2)

Also known as: MK-3475, Keytruda

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab); Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

SD-101 DRUG

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

Also known as: Toll-like receptor 9

Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

Leuprolide acetate DRUG

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.

Also known as: Intermittent androgen deprivation therapy

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab); Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

Abiraterone Acetate DRUG

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.

Also known as: Intermittent androgen deprivation therapy

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab); Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

Prednisone DRUG

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.

Also known as: Intermittent androgen deprivation therapy

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab); Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

Stereotactic Body Radiation Therapy RADIATION

7 Gy x 5 fractions (35 Gy total) 1-2 weeks after fiducial marker placement and simulation over 10-14 days.

Also known as: SBRT

Cohort 2, Arm 1: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab); Cohort 2, Arm 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be \>=18 years of age on day of signing informed consent.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Histologically documented adenocarcinoma of the prostate
• Oligometastatic disease. In order to be eligible, the participant must have a total of \<4 metastatic bone and/or metastatic lymph node sites based on bone and/or soft tissue lesions as defined by any of the following:
• Bone metastases will be defined by bone imaging. If the participant has technetium bone scan, and/or sodium fluoride (NaF) PET performed, either study may be used for documenting metastases; both scans do not need to show the number of metastases required for study entry. For participants undergoing PSMA PET, only PSMA avid lesions that are consistent with metastasis will be counted as a site of metastasis.
• Distant metastatic lymph node disease. A lymph node ≥1 cm in shortest dimension will be noted as involved with disease. Distant metastatic lymph nodes will be determined as any lymph nodes outside the confines of the true pelvis. For participants undergoing PSMA PET, only PSMA avid lesions that are consistent with metastasis will be counted as a site of metastasis.
• Any other soft tissue lesion deemed by the physician to be consistent with distant metastatic disease. For participants undergoing PSMA PET, only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
• Note: Radiographic imaging performed as standard of care prior to obtaining informed consent and within 60 days of initiating study treatment may be used to assess oligometastatic disease during screening, rather than repeating scans. For participants who have started on ADT, they must have had imaging prior to initiation of hormonal therapy
• Treatment naïve, defined as less than 2 months of standard of care ADT (e.g. GnRH agonist or antagonist with or without antiandrogen, including abiraterone) for metastatic hormone-sensitive prostate cancer prior to enrollment (at the time of consent)
• No prior chemotherapy for prostate cancer
• Not a candidate for or refuse chemotherapy
• No prior prostatectomy or prostatic radiation
• PSA \>2 ng/mL at baseline or prior to initiation of hormonal therapy
• Baseline testosterone \>150 ng/dL if participant has not initiated hormonal therapy, for those participants who have already initiated hormonal therapy, baseline testosterone is not required

You may not qualify if:

• Participants who are not appropriate candidates for prostate or oligometastasis-directed SBRT
• Participants with neuroendocrine or small cell features are not eligible.
• Participants with evidence of liver metastasis are excluded.
• Gonadotropin-releasing hormone (GnRH) agonists or GnRH antagonists (e.g., leuprorelin, degarelix) for \> 2 months prior to consenting
• Antiandrogens (e.g., bicalutamide, flutamide, nilutamide, abiraterone, enzalutamide) for \> 2 months prior to consenting. Participants on 5-alpha reductase inhibitors are allowed on study.
• Estrogen containing compounds for \> 2 months prior to consenting
• PC-SPES or PC-x products. Other herbal therapies or supplements will be considered by the Principle Investigator on a case-by-case basis based on their potential for hormonal or anti-cancer therapies.
• Prior immunotherapy or chemotherapy for prostate cancer
• Prior radiation therapy to the prostate
• Prior prostatectomy
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment, with the exception of steroids for adrenal insufficiency in which case prednisone =\<10mg/day or its equivalent is allowed.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• TriSalus Life Sciences, Inc.: collaborator
• David Oh: lead
• Prostate Cancer Foundation: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab; Toll-Like Receptor 9; Leuprolide; Abiraterone Acetate; Prednisone; Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

DNA-Binding Proteins; Proteins; Amino Acids, Peptides, and Proteins; Toll-Like Receptors; Receptors, Pattern Recognition; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. David Oh, MD, PhD
• Organization: University of California, San Francisco

David.Oh@ucsf.edu

(415) 476-1000

Study Officials

• David Oh, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: January 2, 2017
• Study Start: May 17, 2017
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: December 5, 2025
• Results First Posted: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)