Darolutamide + Pembrolizumab + Lupron for Prostate Cancer

Overseen By Monali Fatterpekar, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must be taking: Antiretrovirals

Must not be taking: Androgen inhibitors, Checkpoint inhibitors

Disqualifiers: Metastatic disease, Active cardiac disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for men with high-risk localized prostate cancer. The researchers aim to evaluate the effectiveness of these therapies together before and after surgery to potentially improve outcomes. Participants will receive a mix of hormone therapy (Lupron), an androgen receptor blocker (Darolutamide), and an immunotherapy drug (Pembrolizumab). Men with prostate cancer that meets specific criteria, such as a Gleason score of 8 or higher and certain genetic markers, may be eligible. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in prostate cancer therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for Hepatitis B or HIV, you should continue those medications during the study. 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 has shown that the combination of Darolutamide, Pembrolizumab, and Lupron has been tested in people before. Evidence suggests these treatments are generally well-tolerated, with patients usually experiencing manageable side effects. Darolutamide, in particular, demonstrated a good safety record in other prostate cancer studies.

Pembrolizumab, an immune therapy, can sometimes cause immune-related side effects. However, it is a widely used cancer treatment, and its side effects are well-known and usually manageable. Lupron, a hormone therapy commonly used in prostate cancer treatment, typically has predictable side effects.

Previous studies with these treatments carefully monitored participants for safety. While individual experiences may vary, past human trials have not revealed unexpected safety issues. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of Darolutamide, Pembrolizumab, and Lupron for prostate cancer because it introduces a novel approach to treatment. Unlike traditional therapies that primarily focus on hormone deprivation, Darolutamide is an androgen receptor antagonist that blocks the effects of male hormones more directly. Pembrolizumab, an immunotherapy, helps the immune system identify and attack cancer cells, adding a layer of defense not typically used in prostate cancer treatment. This combination aims to tackle the cancer from multiple angles, potentially improving outcomes for patients with high-risk localized prostate cancer.

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

Research has shown promising results for using Darolutamide, Pembrolizumab, and Lupron together to treat high-risk prostate cancer. In this trial, participants will receive a combination of these treatments. Darolutamide, when combined with hormone therapy, significantly extends the time patients live without their cancer worsening. This combination reduces the chance of cancer spreading or causing death by 46%. Pembrolizumab boosts the immune system, helping the body fight cancer cells more effectively. Lupron, a hormone therapy, reduces testosterone levels, which can slow the growth of prostate cancer. These treatments work together to attack cancer from different angles, showing strong potential for success. ^{1 5 6 7 8}

Who Is on the Research Team?

Ashutosh K Tewari, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Dimple Chakravarty, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for men over 18 with high-risk, non-metastatic prostate cancer confirmed by biopsy. Eligible patients have a Gleason score ≥8, PSA >20 ng/ml, or stage ≥cT3a and must show three specific molecular features: Decipher Genomic Classifier >0.6, AR activity score >11, and Luminal B subtype.

Inclusion Criteria

My cancer has three specific molecular features identified at biopsy.

I am a man aged 18 or older.

My Decipher test score is above 0.6.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant ADT, Darolutamide, and Pembrolizumab (5 cycles) prior to radical prostatectomy

17 weeks

Regular visits for treatment administration and monitoring

Surgery

Participants undergo radical prostatectomy to assess residual disease

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive adjuvant Pembrolizumab (12 cycles) post-radical prostatectomy

33 weeks

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes

5 years

Periodic visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Lupron
• Pembrolizumab

Trial Overview The study tests neoadjuvant therapy combining Androgen Deprivation Therapy (ADT), Darolutamide (an AR-antagonist), and Pembrolizumab before surgery in high-risk prostate cancer patients. After surgery, participants receive adjuvant Pembrolizumab for up to 12 cycles.

How Is the Trial Designed?

Group I: Participants with Prostate Cancer Experimental Treatment 3 Interventions

Neoadjuvant ADT plus AR- antagonist, Darolutamide plus Pembrolizumab (5 cycles) prior to radical prostatectomy (RP) in a stratified high-risk localized prostate cancer cohort, followed by adjuvant treatment with Pembrolizumab (12 cycles) post-RP.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

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

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07027124

Neoadjuvant ADT + Darolutamide With Pembrolizumab ... The objectives of this study are to evaluate if the neoadjuvant ADT, Darolutamide and Pembrolizumab treatment in high-risk prostate cancer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11654448/

Darolutamide in Combination With Androgen-Deprivation ... Darolutamide plus ADT significantly improved radiological progression-free survival, reducing the risk of radiological progression or death by 46% versus ...

3. ascopubs.org ascopubs.org/doi/10.1200/OP-24-00690

Real-World Evidence of Combination Therapy Use in ... Overall, 28% received combination therapy with ARPI (18% abiraterone; 10% apalutamide, darolutamide, or enzalutamide), 9% with DOC, and 2.5% ...

4. ichgcp.net ichgcp.net/clinical-trials-registry/NCT07027124

Darolutamide and Pembrolizumab and Lupron in Prostate ... The objectives of this study are to evaluate if the neoadjuvant ADT, Darolutamide and Pembrolizumab treatment in high-risk prostate cancer ...

5. erc.bioscientifica.com erc.bioscientifica.com/view/journals/erc/aop/erc-24-0188/erc-24-0188.pdf

Real-world Effectiveness of Darolutamide in Metastatic ... Darolutamide is a 2nd generation androgen receptor (AR) antagonist (2GARA) with established benefit in treating patients with non-metastatic ...

6. withpower.com withpower.com/trial/phase-2-prostatic-neoplasms-5-2025-61af3

Darolutamide + Pembrolizumab + Lupron for Prostate Cancer Prior Safety DataThis treatment has passed at least one previous human trial ... Participants are monitored for safety, effectiveness, and long-term outcomes.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8909751/

Immune Checkpoint Inhibitors in Advanced Prostate Cancer No survival benefit was observed (mOS 28.7 vs. 29.7, HR 1.1, p = 0.37), but increased median progression-free survival (mPFS) and PSA response ...

8. academic.oup.com academic.oup.com/oncolo/article/29/7/581/7613339

Extended Safety and Tolerability of Darolutamide for ... Darolutamide has demonstrated a consistently favorable safety profile in patients with nmCRPC, mHSPC, and metastatic CRPC from early-phase ...