Chemoimmunotherapy + Hormone Therapy for Prostate Cancer

Overseen By Research Nurse Navigator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mark Stein

Must be taking: 5-alpha reductase inhibitors

Must not be taking: Immunotherapy, Chemotherapy

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for prostate cancer that has spread and still responds to hormone therapy. The research examines the safety and effectiveness of using hormone therapy with chemoimmunotherapy, including drugs like degarelix (a hormone therapy), docetaxel (a chemotherapy drug), leuprolide acetate (another hormone therapy), and REGN2810 (an experimental treatment). The goal is to determine if this combination can reduce prostate-specific antigen (PSA) levels, a marker of prostate cancer, to undetectable levels within six months. Men with newly metastatic, hormone-sensitive prostate cancer who haven't received certain treatments before may qualify for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on androgen receptor inhibitors, you will need to stop them for the duration of the study. If you are taking 5-alpha reductase inhibitors, you should continue them during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that both degarelix and leuprolide acetate have similar safety levels, with serious heart issues being rare as less than 1% of patients experienced significant changes in heart rhythm. Research has also examined docetaxel, a common chemotherapy drug, which can cause side effects like low blood counts and hair loss, though these are usually manageable.

Cemiplimab (also known as REGN2810) is another component of the treatment. As an immunotherapy, it helps the body's immune system fight cancer. Research on cemiplimab, whether used alone or with other treatments, suggests it is generally well-tolerated. Some patients may experience fatigue, skin rash, or diarrhea, but these effects are often mild.

Overall, these treatments have been used in other studies and are considered to have manageable safety profiles. However, since the current trial is in its early stages, researchers are still carefully testing this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this chemoimmunotherapy approach for prostate cancer because it combines hormone therapy with an innovative immunotherapy drug, cemiplimab (REGN2810). Unlike standard treatments which often rely solely on hormone therapy or chemotherapy, this approach uses cemiplimab, an immune checkpoint inhibitor, to help the body's immune system target and attack cancer cells more effectively. Additionally, the treatment protocol includes a sequential administration of degarelix and leuprolide acetate, followed by docetaxel, which aims to maximize the therapeutic impact by strategically timing each component to enhance overall efficacy. This novel combination and sequence of therapies offers a potential new way to tackle prostate cancer, building on the strengths of different treatment modalities.

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

Research has shown promising results for the treatments studied in this trial. Participants will receive a combination of treatments. Degarelix, a drug that lowers testosterone levels, helped 97% of patients maintain low testosterone, crucial for controlling prostate cancer. Studies found that 77% of patients with advanced prostate cancer were still alive three years after starting degarelix. Docetaxel, a chemotherapy drug, reduced prostate cancer deaths by 70% when added to standard treatments. Leuprolide acetate, another hormone therapy, effectively lowers testosterone and PSA levels, important markers for controlling prostate cancer. REGN2810, also known as cemiplimab, has improved survival rates without disease in other cancer types, suggesting it might also help with prostate cancer. Together, these treatments aim to effectively manage and control hormone-sensitive metastatic prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Mark N. Stein

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Men over 18 with newly metastatic, hormone-sensitive prostate cancer who haven't had certain treatments like androgen deprivation therapy or chemotherapy for prostate cancer in the last 6 months. They should have a life expectancy over a year, good organ function, no severe allergies to trial drugs, and agree to use contraception.

Inclusion Criteria

- Platelets ≥100,000

- Leukocytes ≥3,000/microliters (mcL)

I agree to use contraception during and 4 months after the study due to unknown effects on fetuses.

Exclusion Criteria

I have Hepatitis B under control with a viral load under 100 IU/mL.

I have had an organ or bone marrow transplant.

My nerve damage symptoms are mild or not present.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT)

Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months

10 weeks

Chemoimmunotherapy

Start cemiplimab (REGN 2810) 350mg IV every 3 weeks for up to 55 weeks or until intolerable side effects or disease progression. Start docetaxel 75 mg/m2 every 21 days for up to 6 cycles

55 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Degarelix
• Docetaxel
• Leuprolide Acetate
• REGN2810

Trial Overview The trial is testing REGN2810 combined with hormonal therapy (Degarelix or Leuprolide Acetate) and Docetaxel chemotherapy. The goal is to see if this mix can make prostate-specific antigen levels undetectable after six months of treatment.

How Is the Trial Designed?

Group I: ADT Followed by Chemoimmunotherapy Experimental Treatment 4 Interventions

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Degarelix is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Firmagon for:

• Advanced hormone-dependent prostate cancer

Approved in United States as Firmagon for:

• Advanced prostate cancer

Approved in Canada as Firmagon for:

• Hormone-sensitive prostate cancer

Approved in Japan as Firmagon for:

• Prostate cancer

Who Is Running the Clinical Trial?

Mark Stein

Lead Sponsor

Trials

4

Recruited

150+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Docetaxel chemotherapy is a standard first-line treatment for castration-resistant prostate cancer, providing a modest overall survival benefit of 2 months, but patients typically progress to a docetaxel-insensitive phase within 6-9 months.

Emerging therapies like cabazitaxel, sipuleucel-T, and abiraterone show promise for secondary treatment options, highlighting the need for more clinical data to explore various combinations and sequences of therapies for better outcomes in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second line therapy for castration-resistant prostate cancer (CRPC)]. Molitor, B., Börgermann, C.[2021]

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

Sipuleucel-T has shown to improve overall survival by 4 months in patients with castration-resistant prostate cancer, particularly benefiting those with favorable prognostic factors like minimal tumor burden and a Gleason score of ≤7.

New immunomodulatory treatments like ipilimumab and tasquinimod, along with antihormonal drugs such as abiraterone acetate, are emerging as promising options for managing castration-resistant prostate cancer, indicating a shift towards more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. Heidenreich, A.[2021]

Docetaxel is an effective treatment for hormone-refractory prostate cancer (HRPC), showing significant anti-tumor effects as a single agent and even more when combined with other drugs like estramustine.

The FDA approved docetaxel in combination with prednisone in 2004 for advanced metastatic prostate cancer, highlighting its established role in treatment despite the challenge of hormone resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of androgen-independent hormone refractory prostate cancer using docetaxel]. Miyoshi, Y., Uemura, H., Kubota, Y.[2018]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

Recent trials have shown that combining enzalutamide or apalutamide with androgen deprivation therapy (ADT) significantly improves survival in patients with metastatic castration-sensitive prostate cancer, expanding treatment options beyond docetaxel and abiraterone acetate.

Emerging evidence also supports the use of radiotherapy for the primary tumor in metastatic prostate cancer, suggesting a more personalized approach to treatment based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving options in metastatic castration-sensitive prostate cancer. Hamilou, Z.[2021]

Cabazitaxel is an effective second-line chemotherapy for metastatic castration-resistant prostate cancer, but it carries a risk of neutropenic complications, especially in frail elderly patients.

Using prophylactic granulocyte colony-stimulating factor from the first treatment cycle can help improve the safety and efficacy of cabazitaxel, and alternative dosing schedules are being explored to benefit frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. Pobel, C., Auclin, E., Procureur, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7385516/

Efficacy and safety of degarelix in patients with prostate cancer The current study also demonstrated that 97% of the patients in the degarelix group achieved and maintained testosterone castrate levels for 364 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.6_suppl.198

Overall survival of patients with metastatic prostate cancer ... The data indicate that 77% of patients with metastatic disease and PSA > 50 ng/mL who start degarelix treatment are alive after an observation period of 36 ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2785385

Cardiovascular Outcomes of Degarelix vs Leuprolide for ... Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S258893112100122X

The Efficacy and Safety of Relugolix Compared with ... In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07–0.92). In all efficacy ranking ...

5. ferring.com ferring.com/new-data-demonstrating-long-term-benefits-of-firmagon-degarelix-for-advanced-hormone-dependant-prostate-cancer-published-in-the-journal-of-urology/

New data demonstrating long-term benefits of FIRMAGON ... “The data from the Phase III extension study demonstrate that FIRMAGON® provided prostate cancer patients with fast and effective testosterone ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03951831

Study Details | NCT03951831 | REGN2810 Followed by ... The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8536955/

Real-world Cardiovascular Outcomes Associated With ... To address this question, a Phase 3b RCT comparing the cardiovascular safety of degarelix and leuprolide among patients with prostate cancer and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02663908

Study Details | NCT02663908 | A Trial Comparing ... The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3047399/

Cardiovascular Safety of Degarelix: Results From a 12-Month ... In men with prostate cancer degarelix and leuprolide have similar CV safety profiles. Marked prolongation of the QTc interval was uncommon (1% or less) with ...

10. urotoday.com urotoday.com/clinical-trials/prostate-cancer/142888-a-multi-center-open-label-randomized-phase-3-trial-comparing-the-safety-and-efficacy-of-177lu-psma-i-t-versus-hormone-therapy-in-patients-with-metastatic-castration-resistant-prostate-cancer.html

Clinical Trials in Urology A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer · Condition: ...