REGN5678 +/- Cemiplimab for Prostate Cancer

Recruiting at 41 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must be taking: Anti-androgens, PD-1/PD-L1

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune, Neurodegenerative, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

345 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of the drug REGN5678 (a PSMAxCD28 costimulatory bispecific antibody), either alone or combined with cemiplimab (also known as Libtayo, an immunotherapy drug), for treating prostate cancer. Researchers seek to assess whether these treatments can help the immune system shrink tumors. Participants must have prostate cancer that has spread or become resistant to standard treatments and should have already tried at least two types of previous cancer therapies. The trial will explore how the body reacts to the drugs and measure their presence in the blood. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received any approved systemic therapy within 3 weeks of starting the trial, and certain other treatments must be stopped within specific time frames before the trial begins.

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

Research shows that REGN5678, when combined with cemiplimab, has produced promising results in patients with advanced prostate cancer. Early findings suggest that most people tolerate this combination well. Some side effects occurred, but they were manageable.

Previous studies on cemiplimab have shown it to be effective, with side effects that are usually mild and manageable with medical help.

In summary, both REGN5678 and cemiplimab have undergone earlier trials with encouraging safety results. Those considering joining a trial should know that these treatments have been tested before and are generally well-tolerated. However, as with any medical treatment, discussing potential risks with a doctor is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for prostate cancer, such as hormone therapy, chemotherapy, or surgery, aim to reduce or remove tumors by targeting cancer cells or hormones. But REGN5678, combined with or without cemiplimab, works differently by engaging the body's immune system to fight the cancer. REGN5678 is a bispecific antibody that helps the immune system recognize and destroy cancer cells, which is a novel approach compared to traditional methods. Researchers are particularly excited about cemiplimab, an immune checkpoint inhibitor, which can potentially enhance the immune response initiated by REGN5678. This combination could offer a more targeted and effective treatment option for prostate cancer, potentially leading to better outcomes for patients.

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

Research shows that combining REGN5678 and cemiplimab holds promise for treating advanced prostate cancer. In this trial, participants will receive REGN5678 with or without cemiplimab. Studies indicate that this combination can enhance the immune system's ability to attack cancer cells in patients with prostate cancer that has spread and resists standard hormone treatments. Early results suggest that the treatment is shrinking tumors. Cemiplimab alone has proven effective in other cancers by significantly reducing the chance of recurrence or progression. These findings offer hope that using REGN5678 with cemiplimab could provide a new treatment option for prostate cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with advanced prostate cancer or renal cell carcinoma that has spread and resisted castration treatment. Participants must have a specific protein on their tumors, have tried certain therapies without success, and cannot have had prior PSMA-targeting therapy or recent biologic treatments. They should not be battling uncontrolled infections like HIV or hepatitis, nor have serious neurological conditions.

Inclusion Criteria

I have received at least 2 doses of 177Lu-PSMA-617 for my cancer.

My prostate cancer has spread, is resistant to hormone therapy, and my PSA is 4 or higher.

I have prostate cancer and have had at least 2 treatments, including a newer hormone therapy.

Exclusion Criteria

I've had cancer treatment within the last 3 weeks or am still recovering from its side effects.

I have received treatment targeting PSMA before.

I do not have an uncontrolled HIV, hepatitis B or C, or an immunodeficiency.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine a safe dose(s) of REGN5678 when given alone or in combination with cemiplimab

Up to 42 days per dose level

Multiple visits for dose administration and monitoring

Dose Expansion

Use the REGN5678 drug dose(s) found in Part 1 to evaluate effectiveness in shrinking tumors

Up to 5 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• REGN5678

Trial Overview The study tests REGN5678 alone and combined with Cemiplimab to see how they affect tumor size in patients with metastatic cancers. Part 1 finds safe doses of REGN5678; Part 2 checks the effectiveness at those doses. Sarilumab may also be given to some participants as part of the study.

How Is the Trial Designed?

Group I: mCRPC - dose expansion cohort Experimental Treatment 2 Interventions

REGN5678 with or without cemiplimab

Group II: mCRPC - dose escalation cohort Experimental Treatment 2 Interventions

REGN5678 with or without cemiplimab

Group III: ccRCC - dose expansion cohort Experimental Treatment 2 Interventions

REGN5678 with or without cemiplimab

Group IV: ccRCC - dose escalation cohort Experimental Treatment 2 Interventions

REGN5678 with or without cemiplimab

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead 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

Bicalutamide, administered at 150 mg daily, showed some effectiveness in reducing pain and improving symptom status in 52 patients with advanced prostate cancer who had progressed after first-line hormonal therapy, although no complete or partial responses were observed.

About 20% of patients experienced a significant decrease in prostate-specific antigen levels, but this did not correlate with symptom improvement, and the most common side effects included hot flashes and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of bicalutamide in patients with advanced prostate cancer in whom conventional hormonal therapy failed: a Southwest Oncology Group study (SWOG 9235). Kucuk, O., Fisher, E., Moinpour, CM., et al.[2022]

Sipuleucel-T is currently the only approved immunotherapy for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer, showing only modest improvements in overall survival, highlighting the challenges of effective immunotherapy in this cancer type.

Recent strategies aim to convert prostate cancer from a 'cold' tumor to a 'hot' tumor, with ongoing clinical trials exploring immune checkpoint inhibitors and combinations with other therapies, indicating a potential shift in treatment efficacy for metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer. Rathi, N., McFarland, TR., Nussenzveig, R., et al.[2021]

In a large registry study involving 1976 patients with metastatic castration-resistant prostate cancer, sipuleucel-T immunotherapy demonstrated a median overall survival of 30.7 months, indicating its potential effectiveness in prolonging life for this patient group.

The treatment was associated with a low incidence of serious adverse events (3.9%) and cerebrovascular events (2.8%), suggesting that sipuleucel-T is a relatively safe option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. Higano, CS., Armstrong, AJ., Sartor, AO., et al.[2021]

Sipuleucel-T is the first FDA-approved immunotherapy that has been shown to improve survival in patients with asymptomatic or minimally-symptomatic metastatic castrate-resistant prostate cancer (mCRPC).

The approval of sipuleucel-T was based on three randomized controlled trials, and ongoing research is exploring its use in combination with other treatments and in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the role of sipuleucel-T in the treatment of patients with advanced prostate cancer? An update on the evidence. Hu, R., George, DJ., Zhang, T.[2020]

Prostate carcinoma (PC) is a challenging cancer to treat, especially after it becomes resistant to androgen deprivation therapy, with current T cell-based immunotherapies like CAR-T cells and bispecific antibodies (bsAbs) showing limited success in solid tumors.

Bispecific antibodies, which can be produced more easily than CAR-T cells, are being developed for PC treatment, but their effectiveness is still under evaluation in clinical trials, highlighting the need for innovative approaches in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives. Heitmann, JS., Pfluegler, M., Jung, G., et al.[2021]

The novel bispecific antibody CC-1 targets prostate-specific membrane antigen (PSMA) on prostate cancer cells and tumor vessels, aiming to provide a dual anticancer effect in patients with metastatic castration-resistant prostate cancer (CRPC) after failing third-line therapy.

This first-in-human clinical trial involves a dose escalation phase to determine the maximum tolerated dose and safety, followed by a dose expansion phase to assess initial efficacy, with a total of at least 15 patients receiving the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma. Heitmann, JS., Walz, JS., Pflügler, M., et al.[2021]

Monoclonal antibodies targeting prostate-specific antigens show promising results in treating advanced prostate cancer, with some studies indicating positive responses in PSA levels and pain relief, based on a systematic review of 12 trials.

Despite the potential benefits of immunotherapy, the overall effectiveness and safety remain debated, highlighting the need for further research and careful consideration of risks and benefits for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Passive-specific immunotherapy with monoclonal antibodies for prostate cancer: A systematic review. Khalili, N., Keshavarz-Fathi, M., Shahkarami, S., et al.[2021]

Targeted therapies for prostate cancer have focused on the androgen receptor, with androgen ablation therapy showing significant improvements in survival rates over the past decade.

While various treatments, including antibody-directed therapies and vaccines targeting prostate-specific proteins, have been developed, the success of pathway inhibitors has been limited due to the absence of a common oncogenic mutation in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies for prostate cancer. Asatiani, E., Gelmann, EP.[2019]

Citations

1. targetedonc.com targetedonc.com/view/unpacking-the-data-behind-adjuvant-cemiplimab-s-fda-approval

Unpacking the Data Behind Adjuvant Cemiplimab's FDA ... The 24-month DFS rates for cemiplimab and placebo treatment were 87.1% and 64.1%, respectively. This effect was observed across all tumor ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9533

CemiplimAb-rwlc survivorship and epidemiology (CASE) Median PFS was 14.7 (95% CI: 12.5, 21.1) months, with survival at 12 months estimated at 59.5% (95% CI: 51.4, 66.7). Treatment-related irAEs ...

3. onclive.com onclive.com/view/adjuvant-cemiplimab-approval-redefines-management-of-high-risk-cscc

Adjuvant Cemiplimab Approval Redefines Management of ... [Specifically, cemiplimab reduced the risk of recurrence or death by 68% compared with placebo (HR, 0.32), which is among the most impressive ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT064/761392/Abstract-CT064-Updated-safety-and-efficacy-results

Abstract CT064: Updated safety and efficacy results from a ... In preliminary analyses, encouraging survival outcomes were observed with the higher nezastomig DLs plus cemiplimab.

5. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... 21.1-month median OS versus 12.9 months, representing a 34% reduction in the risk of death (hazard ratio [HR]: 0.66; 95% confidence interval [ ...

6. onclive.com onclive.com/view/regn5678-plus-cemiplimab-demonstrates-early-activity-in-mcrpc

REGN5678 Plus Cemiplimab Demonstrates Early Activity ... The results showed that the higher dose levels evaluated in cohorts 6 through 8 were associated with improved anti-tumor activity within 6 weeks ...

7. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/updated-libtayor-cemiplimab-rwlc-results-reinforce-durable-and

Updated Libtayo® (cemiplimab-rwlc) Results Reinforce ... "The data presented at this meeting offer longer-term results in more than twice as many patients as initially reported for the Phase 2 trial at ASCO last year ...