Pembrolizumab + Therapy for Metastatic Prostate Cancer

Overseen By Lawrence Fong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David Oh

Must be taking: GnRH agonists, GnRH antagonists

Must not be taking: Estrogens, Immunosuppressants

Disqualifiers: Liver metastasis, Immunodeficiency, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 21

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a combination of therapies for metastatic prostate cancer that has not been treated with hormones. The trial examines the effectiveness of stereotactic body radiation therapy (a precise form of radiation), pembrolizumab (a type of immunotherapy), and possibly SD-101 (an experimental treatment) together. Participants will receive these treatments to determine their effectiveness in managing cancer that has spread to a few locations beyond the prostate. This trial may suit those newly diagnosed with prostate cancer that has spread to fewer than four other areas and have not yet undergone extensive cancer treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that certain hormonal therapies and immunosuppressive treatments should not have been used recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pembrolizumab is generally well-tolerated by patients with prostate cancer. Studies have found it safe for men with advanced prostate cancer that no longer responds to hormone therapy. Common side effects include tiredness and skin reactions, which are usually manageable.

Early studies have also shown that SD-101 is well-tolerated. It may help the immune system better identify and attack cancer cells. While more research is needed, early results suggest promising effects on the immune system with manageable side effects.

Both treatments remain under study, and current trial phases indicate they are safe enough for testing in people. Participants should discuss potential risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic prostate cancer because they combine several innovative approaches with existing therapies. Unlike traditional treatments that mainly focus on hormonal therapy, this trial explores the addition of Pembrolizumab, an immunotherapy drug, which helps the immune system target cancer more effectively. Furthermore, the trial includes a novel TLR9 agonist, SD-101, which aims to enhance the immune response directly within the tumor. Lastly, the use of stereotactic body radiation therapy (SBRT) offers precise targeting of cancerous sites, potentially reducing side effects compared to conventional radiation therapy. These features could lead to more effective and comprehensive cancer control.

What evidence suggests that this trial's treatments could be effective for metastatic prostate cancer?

Research has shown that pembrolizumab, one of the treatments in this trial, may help treat prostate cancer. In earlier studies, it significantly benefited patients with advanced prostate cancer who had already received many treatments. Some patients experienced a quick slowdown in cancer growth with pembrolizumab.

Studies have found that SD-101, another treatment option in this trial, strengthens the immune system when combined with radiation therapy. Specifically, SD-101 increases the number of immune cells that can kill cancer cells. This combination has been effective for some prostate cancer patients, leading to positive results based on PSA (prostate-specific antigen) levels.

These findings suggest that both pembrolizumab and SD-101, as part of different treatment arms in this trial, might help treat prostate cancer by boosting the body's ability to fight the disease. ^{1 2 6 7 8}

Who Is on the Research Team?

David Y Oh, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men over 18 with newly diagnosed hormone-naive oligometastatic prostate cancer, who haven't had chemotherapy or surgery for it, and have fewer than four metastases. They must be able to consent, have good organ function and performance status (able to carry out daily activities), agree to use contraception, and not be on certain other treatments.

Inclusion Criteria

My cancer has spread to my bones, confirmed by a bone scan.

Your kidney function should be measured according to the hospital's rules.

My hemoglobin level is at least 9 g/dL without needing transfusions or EPO recently.

Exclusion Criteria

I have had surgery to remove my prostate.

I have been on antiandrogens for more than 2 months.

I have had radiation therapy to my prostate before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT) Run-in

Three month androgen deprivation therapy (ADT) run-in followed by leuprolide injected intramuscularly every 3 months for 3 doses

3 months

Regular visits for injections

Treatment

Participants receive pembrolizumab IV every 21 days for up to 13 doses, stereotactic body radiation therapy (SBRT) every other day over 10-14 days, and optional SD-101 injections

9 months

Pembrolizumab every 21 days, SBRT every other day for 10-14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Leuprolide acetate
• Pembrolizumab
• Prednisone
• SD-101

Trial Overview The trial is testing the combination of radiation therapy and pembrolizumab immunotherapy with or without SD-101 injected into tumors in patients with limited-spread prostate cancer. It's an open-label Phase 2 study where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Cohort 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab, SD-101) Experimental Treatment 6 Interventions

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.

Group II: Cohort 2: Prostate and Oligometastatic sites (ADT, SBRT, Pembrolizumab) Experimental Treatment 5 Interventions

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.

Group III: Cohort 1: Prostate Only Sites (ADT, SBRT, Pembrolizumab, SD-101) Experimental Treatment 6 Interventions

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.

Group IV: Cohort 1: Prostate Only Sites (ADT, SBRT, Pembrolizumab) Experimental Treatment 5 Interventions

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.

Who Is Running the Clinical Trial?

David Oh

Lead Sponsor

Trials

2

Recruited

50+

Lawrence Fong

Lead Sponsor

Trials

6

Recruited

90+

Dynavax Technologies Corporation

Industry Sponsor

Trials

30

Recruited

17,800+

TriSalus Life Sciences, Inc.

Industry Sponsor

Trials

10

Recruited

420+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1558767325000849

Clinical Outcomes of Patients With Metastatic Prostate ... Treatment with pembrolizumab led to a significant rate of biochemical and radiographic response in a heavily pre-treated cohort of MSI-H metastatic prostate ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02861573

NCT02861573 | Study of Pembrolizumab (MK-3475) ... The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combination therapy in participants with metastatic castration ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7186583/

Pembrolizumab for Treatment-Refractory Metastatic Castration ... Initial results from the first 10 patients with enzalutamide-resistant mCRPC who were treated with pembrolizumab in a phase II study showed a rapid decrease in ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.165

Updated results of a phase Ib single-center study ... This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)34146-8/fulltext

Pembrolizumab for advanced prostate adenocarcinoma Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02787005

Study of Pembrolizumab (MK-3475) in Participants With ... This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC). Participants will be enrolled into ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00199-1/fulltext

the randomized, double-blind, phase III KEYNOTE-641 study The study evaluated pembrolizumab plus enzalutamide for chemotherapy-naive metastatic castration-resistant prostate cancer.

8. merck.com merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf

keytruda_pi.pdf Of the 564 patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin, 44% (n=247) were 65 ...