Pembrolizumab + Hormone and Radiation Therapy for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must be taking: Androgen deprivation therapy

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infection, HIV, 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: 18

Duration: 24 months

32 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

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

What data supports the effectiveness of the drug pembrolizumab in treating prostate cancer?

Some studies have shown that pembrolizumab, a drug that helps the immune system fight cancer, can reduce tumor size in certain prostate cancer patients, especially those with specific genetic markers. However, its overall effectiveness in prostate cancer has been inconsistent, with some trials not showing significant benefits. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and hormone therapy safe for prostate cancer treatment?

Pembrolizumab, used in various cancers, has shown some common side effects like fatigue, nausea, and rash, and more serious immune-related effects like thyroid issues and lung inflammation. In prostate cancer studies, some patients experienced immune-related side effects, but these were not linked to treatment response. ^{1 2 6 7 8}

How is the drug pembrolizumab unique for prostate cancer treatment?

Pembrolizumab is unique for prostate cancer treatment because it is an immune therapy that targets PD-1, a protein on immune cells, to help the body's immune system attack cancer cells. It has shown unexpected antitumor activity in some patients with advanced prostate cancer, especially those who have not responded to other treatments. ^{1 2 5 9 10}

What is the purpose of this trial?

This phase II trial tests how well pembrolizumab along with standard of care androgen deprivation therapy, with bicalutamide and gonadotropin releasing hormone agonist, and radiotherapy for the treatment of patients with high risk prostate cancer that has not spread to other parts of the body (localized). A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Bicalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of tumor cells. Gonadotropin-releasing hormone agonists prevent the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate cancer cells that need testosterone to grow. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving pembrolizumab with androgen deprivation therapy and radiotherapy may kill more tumor cells in patients with high risk localized prostate cancer.

Research Team

Mark G Garzotto

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

Men with high-risk localized prostate cancer that hasn't spread are eligible for this trial. They must not have had prior treatments and should be suitable for hormone therapy and radiotherapy. Specific medical conditions or medications may exclude participation.

Inclusion Criteria

I am 18 or older with a new diagnosis of high-risk, non-spreading prostate cancer.

I am fully active or can carry out light work.

I meet the requirements for hepatitis B or C.

Exclusion Criteria

I have active brain metastases or carcinomatous meningitis.

I am currently being treated for an infection.

I have been diagnosed with HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab IV every 3 weeks for 51 weeks, standard of care ADT for 24 months, and bicalutamide for 6 to 24 months, along with radiotherapy

24 months

17 visits (in-person) for pembrolizumab, additional visits for ADT and radiotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Yearly visits (in-person)

Treatment Details

Interventions

• Androgen Deprivation Therapy
• Pembrolizumab
• Radiotherapy

Trial Overview The study is testing pembrolizumab (a monoclonal antibody) combined with standard hormone therapies and radiotherapy to see if it's more effective in treating prostate cancer than the current standard care alone.

Participant Groups

Group I: Treatment (Pembrolizumab, ADT, radiotherapy) Experimental Treatment 10 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for 51 weeks in the absence of disease progression or unacceptable toxicity. Patients receive standard of care ADT with GNRH agonist (leuprolide, goserelin, triptorelin) or GNRH antagonist (relugolix, degarelix) for a total of 24 months, bicalutamide PO QD for 6 months or up to 24 months per the discretion of the treating physician and radiation therapy per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo bone scan and/or CT scan/MRI during screening and prostate biopsy and blood sample collection throughout the study.

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+

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

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

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]

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 1346 prostate cancer patients, only 3.1% were found to have microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, indicating that this molecular phenotype is rare but significant for treatment options.

Among 11 patients with MSI-H/dMMR castration-resistant prostate cancer who received anti-PD-1/PD-L1 therapy, 54.5% experienced a significant decline in prostate-specific antigen levels, suggesting that this therapy can be effective for some patients with this specific tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. Abida, W., Cheng, ML., Armenia, J., 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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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 a phase III study involving 793 participants with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), the combination of pembrolizumab and olaparib did not significantly improve radiographic progression-free survival (rPFS) or overall survival (OS) compared to next-generation hormonal agents (NHA).

Although the combination therapy showed a higher objective response rate (16.8% vs. 5.9% for NHA), the study was ultimately stopped for futility, indicating that it did not provide a meaningful benefit in prolonging survival or delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. Antonarakis, ES., Park, SH., Goh, JC., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

PD-1 Blockade Falls Short (Repeatedly) in Prostate Cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-921: Phase III study of pembrolizumab plus docetaxel for metastatic castration-resistant prostate cancer. [2022]