What side effects are associated with this type of intervention?

Common side effects of treatments for prostate cancer, particularly those involving immune checkpoint inhibitors like pembrolizumab, include fatigue, rash, diarrhea, and pruritus. More severe immune-related adverse events can occur, such as pneumonitis, colitis, hepatitis, endocrinopathies (e.g., hypothyroidism, hyperthyroidism), and nephritis. When pembrolizumab is combined with other therapies like chemotherapy, additional side effects such as nausea, anemia, and neutropenia may also be observed. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

Pembrolizumab, an immune checkpoint inhibitor targeting the PD-1 receptor, has shown promise in various cancers, including metastatic castration-resistant prostate cancer (mCRPC). While specific FDA approvals for pembrolizumab in prostate cancer are not detailed, it is being studied in combination with other therapies such as olaparib, docetaxel, and enzalutamide in clinical trials. Other immune checkpoint inhibitors, like nivolumab, have also been explored in prostate cancer, but pembrolizumab's role remains investigational pending further trial results.

What other types of research exist?

Promising alternatives to Pembrolizumab for prostate cancer patients include Nivolumab (another PD-1 inhibitor), Atezolizumab (a PD-L1 inhibitor), and combination therapies such as Pembrolizumab with Olaparib, Docetaxel, Enzalutamide, Abiraterone, Lenvatinib, or Belzutifan. These combinations are being evaluated in various cohorts of the KEYNOTE-365 study and other clinical trials.

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Androgen Synthesis Inhibitor

Pembrolizumab Combination Therapies for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments include hormone therapy, chemotherapy, and immune checkpoint inhibitors like pembrolizumab. Hormone therapy reduces androgen levels or blocks their effects, slowing cancer growth. Chemotherapy uses drugs to kill rapidly dividing cells. Immune checkpoint inhibitors, such as pembrolizumab, block the PD-1 receptor on T-cells, enhancing the immune system's ability to attack cancer cells. These treatments are crucial as they offer different mechanisms to control or eliminate cancer, providing options tailored to individual patient needs and improving outcomes.

Phase 1 & 2

Recruiting

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

For Cohorts F, H, I: Has t-NE or de novo metastatic prostate cancer defined by ≥1% neuroendocrine cells that are located in discrete regions of a recent biopsy specimen from a metastasis as determined by the investigational site and confirmed by central histology review prior to enrollment. Epstein criteria of neuroendocrine differentiation in prostate cancer is used for eligibility. Specimens must have one of the morphologies of Small cell carcinoma or Large cell neuroendocrine carcinoma (LCNEC) or Mixed (small or large cell) NE carcinoma - acinar adenocarcinoma with positive IHC confirmed by central pathology review

Has prostate cancer progression within 6 months prior to screening, as determined by the investigator, by means of one of the following: PSA progression as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL; radiographic disease progression in soft tissue based on Response Evaluation Criteria In Solid Tumors Version 1.1 criteria with or without PSA progression; radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression. Participants with de novo neuroendocrine prostate cancer will not need to provide evidence of progression within 6 months

Must not have

Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease

Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests pembrolizumab combined with other drugs in patients with advanced prostate cancer that doesn't respond to usual treatments. The treatment works by boosting the immune system to better attack cancer cells. Pembrolizumab has been previously tested in combination with chemotherapy for other cancers, showing improved response rates and progression-free survival.

Who is the study for?

Men with advanced prostate cancer that's resistant to hormone therapy and has spread, who are still undergoing androgen deprivation (testosterone <50 ng/dL). They must be relatively healthy (ECOG 0-2), able to provide a recent tumor sample, and have had cancer progression within the last 6 months. Participants should agree to contraception if applicable. Those with certain prior treatments or medical conditions like HIV, hepatitis B/C, brain metastases, or intense bone scans aren't eligible.

What is being tested?

The trial is testing how safe and effective pembrolizumab is when combined with other drugs in different groups of patients with metastatic castration-resistant prostate cancer. There are ten cohorts each receiving various combinations including pembrolizumab plus olaparib, docetaxel/prednisone, enzalutamide, abiraterone/prednisone among others.

What are the potential side effects?

Pembrolizumab can cause immune system-related side effects such as inflammation in organs like lungs or intestines; skin reactions; hormonal gland problems; fatigue; infusion reactions; liver issues. Other drugs used may add side effects like nausea, hair loss from chemotherapy or blood clots from hormone therapies.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My prostate cancer biopsy shows specific cell types and has been confirmed by a central review.

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My prostate cancer has worsened in the last 6 months, shown by tests or scans.

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I agree to follow the study's rules for sex and contraception during and after treatment.

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My prostate cancer is confirmed and not of the small cell type.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had lung inflammation that needed steroids or have it now.

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I have not received a live vaccine in the last 30 days.

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I have had a seizure in the last 6 months or am on seizure medication that affects liver enzymes.

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I have severe heart issues like heart failure, unstable chest pain, irregular heartbeat, or high blood pressure.

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I have fluid buildup in my abdomen or around my lungs.

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I have active diverticulitis or other serious abdominal conditions.

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I have not been in a pembrolizumab trial or received PD-1/PD-L1/PD-L2 inhibitors.

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I have been diagnosed with HIV.

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I have or might have cancer spread to my brain or its coverings.

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My blood pressure is either below 86 or above 170/105 mmHg.

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I have serious heart issues, including a recent heart attack or severe angina.

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I have a long-term liver disease.

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My heart's pumping ability is below the normal range.

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I have a condition that affects how my body absorbs medication.

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I had major surgery less than 3 weeks before starting the study treatment.

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I have a severe fistula.

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I haven't had cancer treatment with monoclonal antibodies in the last 4 weeks or have recovered from their side effects.

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I have not had certain cancer treatments or recovered from their side effects in the last 2 weeks.

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I have been treated for an autoimmune disease in the last 2 years.

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I am currently taking medication that strongly affects liver enzyme levels.

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I haven't had major heart problems or strokes in the last year.

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I have coughed up bright red blood recently.

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I have been treated for prostate cancer with platinum-based drugs.

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I am currently taking medications that strongly affect liver enzymes.

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I am currently taking medication for fungus, certain antibiotics, or HIV/AIDS.

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My blood pressure is very high and not under control.

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I have had a transplant of an organ, bone marrow, or solid tissue.

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I have myelodysplastic syndrome.

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My bone scan shows intense activity that makes it hard to see future metastases.

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I stopped taking abiraterone acetate because of side effects.

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I have cancer that has spread to my brain or surrounding membranes.

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I have received radiopharmaceuticals for prostate cancer within the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: Pembrolizumab/Vibostolimab coformulation:t-NEExperimental Treatment1 Intervention

Participants with t-NE mCRPC in Cohort H will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Group II: Pembrolizumab/Vibostolimab coformulationExperimental Treatment1 Intervention

Participants with AC mCRPC in Cohort G will receive a coformulation fixed dose combination of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684) Q3W IV from Day 1 of Cycle 1. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Group III: Pembrolizumab+OlaparibExperimental Treatment3 Interventions

Participants with adenocarcinoma (AC) mCRPC in Cohort A will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week dosing cycle (Q3W) and olaparib 400 mg capsules or 300 mg tablets by mouth (PO) twice a day (BID) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with olaparib will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.

Group IV: Pembrolizumab+Lenvatinib:t-NEExperimental Treatment2 Interventions

Participants with neuroendocrine (t-NE) mCRPC in Cohort F will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Group V: Pembrolizumab+Lenvatinib: ACExperimental Treatment2 Interventions

Participants with AC mCRPC in Cohort E will receive pembrolizumab 200 mg IV on Day 1 Q3W, and lenvatinib 20 mg PO QD continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Group VI: Pembrolizumab+EnzalutamideExperimental Treatment2 Interventions

Participants with AC mCRPC in Cohort C will receive pembrolizumab 200 mg IV on Day 1 Q3W and enzalutamide 160 mg PO every day (QD) continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue until progression or a maximum of 35 treatment cycles (up to 2 years). Treatment with enzalutamide will continue until progression. Participants who must discontinue 1 of the 2 drugs in the combination due to adverse events may continue the study with the other combination drug.

Group VII: Pembrolizumab+Docetaxel+PrednisoneExperimental Treatment4 Interventions

Participants with AC mCRPC in Cohort B will receive pembrolizumab 200 mg IV on Day 1 Q3W, docetaxel 75 mg/m\^2 IV on Day 1 Q3W, and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Participants will only be permitted to receive a maximum of 10 cycles of docetaxel and prednisone. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Group VIII: Pembrolizumab+Carboplatin+EtoposideExperimental Treatment3 Interventions

Participants with neuroendocrine mCRPC in Cohort I Arm 1 will receive pembrolizumab 200 mg IV on Day 1 Q3W + carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 Q3W + etoposide 100 mg/m\^2 IV on Days 1, 2, and 3 Q3W. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 or 2 of the 3 drugs due to adverse events in the combination may continue the study with the other combination drug/drugs.

Group IX: Pembrolizumab+BelzutifanExperimental Treatment2 Interventions

Participants with AC mCRPC in Cohort J will receive belzutifan 120mg QD in the initial cohort. If an efficacy signal is detected in this arm based on a totality of evidence, Cohort J may be expanded further where participants will be randomized 1:1 to receive either belzutifan 120 mg QD or belzutifan 120 mg QD and pembrolizumab 200 mg Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression.

Group X: Pembrolizumab+Abiraterone+PrednisoneExperimental Treatment3 Interventions

Participants with AC mCRPC in Cohort D will receive pembrolizumab 200 mg IV on Day 1 Q3W, abiraterone acetate 1000 mg PO QD and prednisone 5 mg tablet PO BID continuously from Day 1 of Cycle 1. Treatment with pembrolizumab will continue for a maximum of 35 cycles (up to 2 years) or until progression. Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Group XI: Carboplatin+EtoposideExperimental Treatment2 Interventions

Participants with neuroendocrine mCRPC in Cohort I Arm 2 will receive carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 Q3W + etoposide 100 mg/m\^2 IV on Days 1, 2, and 3 Q3W. Treatment will continue for a maximum of 35 cycles (up to 2 years) or until progression. Treatment with carboplatin+etoposide will continue for a maximum of 4 cycles (up to 2.8 months). Participants who must discontinue 1 of the 2 drugs due to adverse events in the combination may continue the study with the other combination drug.

Group XII: BelzutifanExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenvatinib

2017

Completed Phase 4

~2070

Carboplatin

2014

Completed Phase 3

~6120

Prednisone 5 mg

2012

Completed Phase 3

~570

Etoposide

2010

Completed Phase 3

~2960

Pembrolizumab 200 mg

2013

Completed Phase 3

~930

0 / 36Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments include hormone therapy, chemotherapy, and immune checkpoint inhibitors like pembrolizumab. Hormone therapy reduces androgen levels or blocks their effects, slowing cancer growth. Chemotherapy uses drugs to kill rapidly dividing cells. Immune checkpoint inhibitors, such as pembrolizumab, block the PD-1 receptor on T-cells, enhancing the immune system's ability to attack cancer cells. These treatments are crucial as they offer different mechanisms to control or eliminate cancer, providing options tailored to individual patient needs and improving outcomes.