Immunotherapy + Hormone Therapy for Prostate Cancer

(Neo-Red-P Trial)

Overseen By Research Nurse Navigator

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Matthew Dallos

Must be taking: Degarelix

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Metastases, Autoimmune disease, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding a new type of immunotherapy, which helps the immune system fight cancer, to hormone therapy can better prevent prostate cancer from returning after surgery. Researchers aim to determine if combining the new drug, BMS-986218, with the hormone therapy degarelix (also known as Firmagon) is more effective than using degarelix alone. Men with prostate cancer who have scheduled surgery and have not received previous cancer treatments might be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain hormonal therapies or immunosuppressive medications. 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 BMS-986218, when combined with degarelix, appears safe before surgery. One study found that using BMS-986218 with hormone therapy in men with prostate cancer was safe and practical, meaning the treatment did not cause serious side effects that would halt the study.

Degarelix is already approved to lower testosterone, which helps shrink or slow down prostate cancer. It is generally well-tolerated, though some people might experience reactions at the injection site or hot flashes.

In early studies with BMS-986218, researchers examined how the drug works in the body and its safety when used with degarelix. These studies help ensure that side effects are manageable and that the combination does not pose unexpected risks. This information is crucial for anyone considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about these treatments because they combine immunotherapy and hormone therapy in a novel way to tackle prostate cancer. BMS-986218 is an innovative immunotherapy that works by enhancing the body's immune response to detect and destroy cancer cells, which is different from traditional hormone therapies like Degarelix that primarily suppress testosterone to slow cancer growth. This dual approach aims to attack the cancer more aggressively, potentially leading to better outcomes and expanding treatment options for patients with prostate cancer.

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

Research has shown that BMS-986218, a type of immunotherapy, can help treat prostate cancer by targeting and reducing certain cells in the tumor that weaken the immune system. Early studies suggest it activates specific immune cells, potentially boosting the body's ability to fight cancer. In this trial, some participants will receive BMS-986218 with degarelix, a hormone therapy that lowers testosterone. Evidence indicates a significant reduction in immune-suppressing cells in tumors when these treatments are combined. This suggests the combination might be more effective in preventing cancer recurrence compared to hormone therapy alone. These findings are promising, but more research is needed to confirm the benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

Karie Runcie

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Men over 18 with high-risk localized prostate cancer (clinical stage T1c-T3b, N0, M0) who have not had prior treatments for their cancer and are scheduled for radical prostatectomy at Columbia University Irving Medical Center. They must have adequate organ function and agree to use barrier contraception post-treatment. Exclusions include significant heart disease, other cancers within the last 2 years, autoimmune diseases, uncontrolled infections or cardiovascular issues.

Inclusion Criteria

I am mostly active and can care for myself.

Absolute neutrophil count (ANC)>1,500 cells/mm3

Hemoglobin >9.0 g/dL

Exclusion Criteria

I do not have any serious heart conditions.

History of known or suspected autoimmune disease with the following exceptions:

My prostate cancer is not the usual type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive degarelix alone or in combination with BMS-986218 prior to radical prostatectomy

3 weeks

2 visits (in-person)

Surgery

Participants undergo radical prostatectomy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, PSA levels, and immune response post-treatment

42 months

Every 3 months in the first year, every 6 months in the second and third years

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986218
• Degarelix

Trial Overview The trial is testing if adding BMS-986218 (an immunotherapy drug) to degarelix (a testosterone-suppressing medication) before surgery can lower the risk of cancer returning compared to using degarelix alone in men with high-risk localized prostate cancer.

How Is the Trial Designed?

Group I: Safety lead-in Experimental Treatment 1 Intervention

The first 4 subjects enrolled will be given degarelix plus BMS-986218.

Group II: Arm B Experimental Treatment 1 Intervention

BMS-986218 20mg IV every 2 weeks x 2 doses starting 3 weeks prior to radical prostatectomy plus degarelix 240mg SQ x1 dose 2 weeks prior to radical prostatectomy.

Group III: Arm A Active Control 1 Intervention

Degarelix 240mg subcutaneous (SQ) x1 dose 2 weeks prior to radical prostatectomy

Who Is Running the Clinical Trial?

Matthew Dallos

Lead Sponsor

Trials

4

Recruited

140+

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Ferring Pharmaceuticals

Industry Sponsor

Trials

323

Recruited

1,242,000+

Pierre-Yves Berclaz

Ferring Pharmaceuticals

Chief Medical Officer since 2023

MD from the University of Lausanne, PhD in Molecular Biology from the Cincinnati College of Medicine

Jean-Frédéric Paulsen

Ferring Pharmaceuticals

Chief Executive Officer since 2023

Master’s degree in Finance from the London School of Economics and Political Science

Published Research Related to This Trial

Androgen suppression therapy (AST) is the standard treatment for metastatic prostate cancer (PCa), but patients often progress to metastatic castration-resistant prostate cancer (mCRPC), which has limited treatment options.

Current research is exploring various immunotherapy strategies, including combination therapies with chemotherapy and radiation, to overcome the immunosuppressive tumor microenvironment in mCRPC, showing promise in preclinical studies with new approaches like targeting the NKG2D pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, Current, and Future of Immunotherapies for Prostate Cancer. Boettcher, AN., Usman, A., Morgans, A., et al.[2020]

Immunotherapy is emerging as a promising treatment for prostate cancer, which is traditionally treated with surgery, radiotherapy, and hormonal therapy, especially for advanced cases where docetaxel-based chemotherapy is FDA-approved and shows significant survival benefits.

Recent developments in prostate cancer immunotherapy, including dendritic cell vaccines and immune checkpoint inhibitors, have shown potential for targeted tumor destruction with less systemic toxicity, although these benefits are still being evaluated in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update: immunological strategies for prostate cancer. Drake, CG., Antonarakis, ES.[2021]

Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 agents, are promising new treatments for prostate cancer, targeting both innate and adaptive immune responses.

Combining these immunotherapies with standard treatments like anti-androgen therapy, chemotherapy, or radiation may enhance their effectiveness in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Immunotargets and Immunotherapies in Prostate Cancer. Montironi, R., Santoni, M., Sotte, V., et al.[2019]

Prostate cancer, once metastatic, is currently treated with a standard regimen of docetaxel and prednisone, but there is growing interest in immunotherapy options, including vaccines and monoclonal antibodies, which may enhance treatment effectiveness.

Recent phase III clinical trials suggest a need to change how we measure the success of immunotherapy, advocating for overall survival and immune response as key endpoints instead of just tumor size, which may not accurately reflect patient benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in prostate cancer: review of the current evidence. Fernández-García, EM., Vera-Badillo, FE., Perez-Valderrama, B., et al.[2022]

Immunotherapy has shown promise in treating various cancers, but prostate cancer has lagged behind, with only one FDA-approved agent (sipuleucel-T) and limited success in improving survival rates for advanced cases.

Recent advancements in immunotherapy strategies, including targeting T cells and modifying the tumor microenvironment, suggest that there is potential for improved outcomes in prostate cancer, especially as new combinations of therapies are being tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for prostate cancer: False promises or true hope? Rekoske, BT., McNeel, DG.[2018]

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11419205/

Fc-enhanced anti-CTLA-4 depletes tumor-infiltrating ... Mechanistic studies indicated BMS-986218 depleted TI-Tregs by engaging CD16a/FCGR3A on tumor macrophages, modulated dendritic cells (DCs), and ...

2. researchgate.net researchgate.net/publication/379636841_Abstract_CT137_Efficacy_and_immunological_outcomes_of_non-fucosylated_anti-CTLA-4_BMS-986218_degarelix_acetate_vs_degarelix_acetate_alone_in_men_with_high-risk_localized_prostate_cancer_Neo-Red-P

Abstract CT137: Efficacy and immunological outcomes of ... The primary endpoint was the safety and feasibility of neoadjuvant BMS-986218 in prostate cancer. Secondary endpoints included the pathologic complete response ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05169684

NCT05169684 | A Study of BMS-986218 or ... The purpose of this study is to assess the safety, efficacy, tolerability, and toxicity of docetaxel alone, in combination with BMS-986218, or in combination ...

4. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT137/742550/Abstract-CT137-Efficacy-and-immunological-outcomes

Abstract CT137: Efficacy and immunological outcomes of non ... The primary endpoint was the safety and feasibility of neoadjuvant BMS-986218 in prostate cancer. Secondary endpoints included the pathologic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04301414

Study Details | NCT04301414 | Non-fucosylated Anti-CTLA ... The purpose of this study is to see whether immunotherapy with BMS-986218 added to degarelix (which suppresses testosterone) given prior to surgery can ...

6. withpower.com withpower.com/trial/early-phase-1-prostatic-neoplasms-1-2020-67eef

Immunotherapy + Hormone Therapy for Prostate Cancer This trial is testing if adding a new drug (BMS-986218) to a hormone therapy (degarelix) before surgery can better prevent prostate cancer from returning.

7. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/54185/pdf

Phase 1/2a First-In-Human Study of BMS-986218 ... Blockade of CTLA-4 by ipilimumab has demonstrated anti-tumor activity in other malignancies, including lung, prostate cancer, and renal cell ...