Pembrolizumab for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must be taking: LHRH agonists

Must not be taking: Denosumab, Steroids

Disqualifiers: Immunodeficiency, Brain metastases, Autoimmune, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of pembrolizumab for prostate cancer that has spread and continues to grow despite low testosterone levels, even after enzalutamide treatment. Pembrolizumab, a monoclonal antibody, may help stop tumor growth by targeting specific cells. The trial consists of an initial treatment phase, a monitoring phase, and a retreatment phase, with pembrolizumab administered every three weeks. Men with metastatic prostate cancer that progresses on enzalutamide might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you must continue taking enzalutamide and LHRH therapy. Some medications, like denosumab, are prohibited, and you should not have had certain treatments like chemotherapy or monoclonal antibodies recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally well-tolerated by patients with prostate cancer. Studies have found that pembrolizumab alone is safe for those with advanced prostate cancer that doesn't respond to hormone therapy. While some patients might experience side effects, they are usually manageable.

In one study, pembrolizumab was tested on patients with advanced prostate cancer, and 38.9% of them experienced significant drops in their prostate-specific antigen (PSA) levels, a positive outcome. The treatment did not cause severe problems for most participants, suggesting it is fairly safe.

Another study combined pembrolizumab with chemotherapy and showed promising safety results in patients with certain types of prostate cancer. This adds to the evidence that pembrolizumab is generally safe for treating prostate cancer.

Overall, the FDA has approved pembrolizumab for other conditions, providing extensive safety data. However, like any treatment, there is always a possibility of side effects, so discussing all risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because, unlike traditional prostate cancer treatments like enzalutamide, it harnesses the power of the immune system to fight cancer cells. Most treatments for prostate cancer work by targeting hormones or specific proteins, but pembrolizumab is a type of immunotherapy known as a checkpoint inhibitor. It blocks a protein called PD-1, which can help the immune system recognize and attack cancer cells more effectively. Researchers are excited about pembrolizumab because it offers a different approach by potentially enhancing the body's natural defenses to combat prostate cancer.

What evidence suggests that pembrolizumab might be an effective treatment for prostate cancer?

Research shows that pembrolizumab might help treat prostate cancer that has spread and doesn't respond to standard testosterone-lowering treatments. In earlier studies, patients with a difficult-to-treat type of metastatic prostate cancer experienced significant improvements with pembrolizumab. Specifically, initial results showed a quick drop in cancer markers in patients who hadn't responded to other treatments. In this trial, participants will receive pembrolizumab alongside enzalutamide. Previous studies have shown promising results in lowering prostate-specific antigen (PSA) levels, which might indicate the cancer is slowing down. These findings suggest pembrolizumab could offer new hope for patients with advanced prostate cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Julie Graff, M.D.

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer that has spread and doesn't respond to low testosterone or enzalutamide treatment. They must have good blood counts, liver and kidney function, be willing to use contraception, and not have had certain other treatments recently.

Inclusion Criteria

My kidney function is within the required range for the study.

My blood clotting time is normal or managed if I'm on blood thinners.

My prostate cancer is confirmed and not purely small cell type.

Exclusion Criteria

I have been diagnosed with HIV.

I do not have an active severe autoimmune disease needing strong treatment in the last 3 months.

My cancer is quickly worsening, and my doctor thinks docetaxel could help.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Patients receive pembrolizumab IV over 30 minutes on day 1, repeating every 3 weeks for 4 courses, alongside standard of care enzalutamide

12 weeks

4 visits (in-person)

Monitoring

Patients continue to receive standard of care enzalutamide daily for the duration of the trial

Retreatment

Patients with disease response or stability receive pembrolizumab IV over 30 minutes on day 1, repeating every 3 weeks for an additional 4 courses, alongside standard of care enzalutamide

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2.5 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests pembrolizumab's effectiveness in patients whose prostate cancer continues to grow after enzalutamide treatment. Pembrolizumab is a monoclonal antibody designed to block tumor growth by targeting specific cells.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 3 Interventions

INITIAL TREATMENT PHASE: Patients who are progressing on enzalutamide will receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily. MONITORING PHASE: After completion of the initial treatment phase, patients continue to receive standard of care enzalutamide PO daily for the duration of the trial. RETREATMENT PHASE: Patients with disease response or stability after the initial treatment phase will receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for an additional 4 courses in the absence of disease progression or unacceptable toxicity. Patients continue to receive standard of care enzalutamide PO daily for the duration of the trial.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Collins Medical Trust

Collaborator

Trials

6

Recruited

410+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

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

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a phase II trial involving men with metastatic castration-resistant prostate cancer (mCRPC) who were progressing on enzalutamide, the anti-PD-1 antibody pembrolizumab showed unexpected antitumor activity, with three out of ten patients achieving significant reductions in prostate-specific antigen (PSA) levels.

The presence of immune cell infiltrates and PD-L1 expression in tumor biopsies from responders suggests that certain biological markers may predict the effectiveness of PD-1 inhibitors in prostate cancer, warranting further investigation into this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Graff, JN., Alumkal, JJ., Drake, CG., et al.[2022]

In a study of 54 men with advanced prostate cancer treated with pembrolizumab, about 55% experienced stabilization or a decline in PSA levels, indicating modest efficacy of the treatment.

Men who started pembrolizumab with lower PSA levels and fewer bone metastases had a higher likelihood of responding to the treatment, suggesting that earlier intervention may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer. Higa, J., Wilenius, K., Savino, S., et al.[2021]

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. 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 ...

3. 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 ...

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(25)00199-1/fulltext

the randomized, double-blind, phase III KEYNOTE-641 study The PSA response rate (95% CI) was 49.0% (44.9% to 53.1%) with pembrolizumab plus enzalutamide versus 45.1% (41.1% to 49.2%) with placebo plus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11892552/

Response to pembrolizumab in advanced prostate cancer ... We found that 38.9% of patients showed a 50% or greater decline in PSA, all of whom had high microsatellite instability (MSI-H). One patient ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02787005

NCT02787005 | Study of Pembrolizumab (MK-3475) in ... This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC).