Pembrolizumab for Prostate Cancer

(CHOMP Trial)

Recruiting at 15 trial locations

Overseen By Matthew B Rettig, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: GnRH analogs

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Brain metastases, 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

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: 7

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, a medication that helps the immune system fight cancer, to determine its effectiveness for Veterans with advanced prostate cancer unresponsive to other treatments. The focus is on patients whose cancer has specific genetic changes related to DNA repair issues (mismatch repair deficiency) or changes in the CDK12 gene. The trial aims to understand the frequency of these genetic changes and how pembrolizumab affects cancer progression and patients' overall health. Veterans with advanced prostate cancer who have undergone certain treatments and possess these specific genetic changes might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you must complete any anti-neoplastic therapies for prostate cancer more than 2 weeks before starting the trial, and chemotherapy more than 4 weeks before. Herbal and non-herbal products that may decrease PSA levels are not allowed, except for medical castration and megestrol for hot flashes.

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

Research shows that pembrolizumab is generally well-tolerated by people with advanced prostate cancer that no longer responds to hormone therapy. Past studies found pembrolizumab to be safe for patients with this type of cancer. Some patients experienced side effects, but these were often manageable. The most common side effects included tiredness, skin rash, and itching. Serious side effects were less common and included inflammation in organs.

Pembrolizumab is a treatment called a checkpoint inhibitor, which helps the immune system fight cancer cells. The FDA has already approved this treatment for other types of cancer, indicating its safety is well-studied.

In summary, while pembrolizumab can cause some side effects, research suggests it is generally safe for treating prostate cancer. Always consult with a healthcare provider for personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Pembrolizumab is unique because it targets the immune system in a way that's different from other prostate cancer treatments. Most standard treatments for metastatic castration-resistant prostate cancer (mCRPC) focus on inhibiting androgen receptor signaling. However, pembrolizumab is a checkpoint inhibitor, which means it helps the immune system recognize and attack cancer cells. Researchers are excited because this immune-based approach could offer new hope for patients whose cancer has progressed despite existing therapies. By targeting specific tumor mutations like dMMR and CDK12-/-, pembrolizumab may provide a more tailored and effective treatment option.

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

Research has shown that pembrolizumab, a type of cancer treatment, may benefit some patients with advanced prostate cancer that no longer responds to hormone therapy. In one study, patients whose cancer did not respond to the drug enzalutamide experienced a quick drop in cancer markers after receiving pembrolizumab. Another study found that pembrolizumab led to significant improvements in patients with a specific genetic marker called MSI-H in their metastatic prostate cancer. However, pembrolizumab has not been effective when combined with chemotherapy for all patients with metastatic prostate cancer. The treatment might work better for those with certain genetic traits, such as mismatch repair deficiency (dMMR). Participants in this trial will receive pembrolizumab as a single treatment arm to evaluate its effectiveness in Veterans with mCRPC who have progressed on at least one prior novel androgen receptor signaling inhibitor. ^{2 3 6 7 8}

Who Is on the Research Team?

Matthew Rettig, MD

Principal Investigator

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Are You a Good Fit for This Trial?

Men with advanced prostate cancer that's resistant to hormone therapy and has specific genetic changes (mismatch repair deficiency or CDK12 inactivation) can join. They must be adults, have a good performance status, agree to use contraception, and not have brain metastases or active infections. Prior treatments for cancer should be completed before joining.

Inclusion Criteria

My prostate cancer is worsening despite low testosterone levels.

I have used AR signaling inhibitors for my prostate cancer.

My liver function tests are within the required range.

Exclusion Criteria

My cancer has spread to my brain.

I have been tested for hepatitis B or C.

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab at 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

Molecular Analysis

Baseline and at-progression biopsies are analyzed for molecular correlates of resistance and sensitivity to pembrolizumab

Throughout the study

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The trial is testing pembrolizumab, an immune checkpoint inhibitor, on its effectiveness against certain types of advanced prostate cancer. It will also compare tumor samples before and after treatment to understand resistance or sensitivity to the drug.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

This is a single-arm, open-label study of the checkpoint inhibitor, pembrolizumab, in Veterans with mCRPC who have progressed on at least 1 prior novel androgen receptor (AR) signaling inhibitor, inclusive of abiraterone acetate, enzalutamide, apalutamide, and darolutamide. In addition to progressive mCRPC, a patient must have a somatic tumor mutation characterized by dMMR or CDK12-/- detected by next generation sequencing (NGS). Patients enrolled in this study will be treated with pembrolizumab at the FDA approved dosage of 200 mg intravenously every 3 weeks (21 days) until disease progression or unacceptable toxicity. During study, patients will maintain a castrate level of testosterone, = 50 ng/dL by ongoing treatment with a GnRH analogue or prior bilateral orchiectomy. Prior to initiating treatment with pembrolizumab, patients will undergo a baseline biopsy of a metastatic lesion. An additional biopsy of a metastatic lesion at the time of progression will be encouraged as well.

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

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

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, 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]

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]

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]

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]

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-24-01283

The Randomized, Double-Blind, Phase III KEYNOTE-921 ... The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38284349/

Pembrolizumab for metastatic castration-resistant prostate ... Expert opinion: Pembrolizumab has not benefitted unselected metastatic prostate cancer patients when combined with chemotherapy, next-generation ...

6. 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35397952/

Long-term Results from the Phase 1b/2 KEYNOTE-365 ... Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide ...

8. 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).