REGN4336 + Cemiplimab for Prostate Cancer

Recruiting at 18 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must be taking: Androgen deprivation therapy

Must not be taking: Corticosteroids, Biologics, Immunosuppressives, others

Disqualifiers: Autoimmune disease, Neurodegenerative disease, Infections, others

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

Compensation: Varies

Number of Visits: Unknown

370 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment called REGN4336 (a PSMAxCD3 bispecific antibody), either alone or combined with other drugs like cemiplimab (Libtayo) or REGN5678, to assess their safety and effectiveness in treating prostate cancer. It specifically targets metastatic castration-resistant prostate cancer (mCRPC), where the cancer has spread and continues to grow despite hormone therapy. Suitable candidates for this trial are those whose prostate cancer has worsened despite treatment with at least two other therapies, including hormone therapy. The trial will monitor side effects and evaluate the treatment's impact on the cancer and the body. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any approved systemic therapy at least 3 weeks before starting the study drugs. If you're on corticosteroids, you need to be on a low dose (10 mg prednisone/day or less) at least 1 week before starting the trial.

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

Research shows that REGN4336 is designed to help the body's T-cells, a type of immune cell, attack cancer cells. Other studies have tested this method, and patients generally handle it well. However, as it remains under study, researchers continue to identify any side effects.

When combined with cemiplimab, REGN4336 aims to boost the immune system's response to cancer. Previous studies suggest this combination is also generally well-tolerated, but researchers closely monitor any negative effects. Cemiplimab already has FDA approval for treating some other cancers, which provides some confidence in its safety.

While early studies suggest these treatments are generally safe, the current trial is crucial for understanding all possible side effects. Participants in the trial will help researchers learn more about how these treatments work and their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, like hormone therapy and chemotherapy, the investigational treatments REGN4336 and Cemiplimab offer a fresh approach by leveraging the body's immune system. REGN4336 targets a specific protein on prostate cancer cells, potentially enhancing the immune system's ability to recognize and attack cancer. Cemiplimab, an immune checkpoint inhibitor, works by preventing cancer cells from evading immune detection. The combination of these therapies could provide a more precise and powerful attack on cancer cells, which is why researchers are hopeful about their potential.

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

Research has shown that REGN4336, a new cancer treatment, may effectively treat prostate cancer. In this trial, some participants will receive REGN4336 alone, while others will receive it with cemiplimab. Earlier studies demonstrated that a similar antibody to REGN4336 caused a quick and significant drop in PSA levels, indicators of prostate cancer, with reductions up to 62%. When combined with cemiplimab, more than half of the patients experienced a PSA level drop of over 50%. This combination enhances the immune system's ability to identify and attack cancer cells. These results suggest that REGN4336, especially when combined with cemiplimab, could effectively lower prostate cancer markers. ^{2 3 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with advanced prostate cancer that's resistant to castration and has worsened despite treatment, including at least one second-generation anti-androgen therapy. Participants must have a PSA level of ≥4 ng/mL and cannot be on high-dose steroids or have had certain recent treatments like systemic biologics, PSMA-targeting therapies, or suffer from significant autoimmune diseases.

Inclusion Criteria

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

My prostate cancer is confirmed but not as a pure small cell type.

My cancer has worsened after 2 or more treatments, including a modern anti-androgen therapy.

Exclusion Criteria

I have an autoimmune disease treated with immune-weakening drugs in the last 5 years.

I haven't taken high doses of steroids or similar medicines in the last week.

I haven't taken any immune therapy (except Sipuleucel-T) recently.

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 of REGN4336 when given alone or in combination with cemiplimab or REGN5678

28 to 42 days

Dose Expansion

Test how well REGN4336 works to shrink tumors either alone or in combination with cemiplimab or REGN5678

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• REGN4336

Trial Overview The trial is testing REGN4336 alone and combined with Cemiplimab to evaluate safety, tolerability, dosage levels (Dose Escalation), and preliminary effectiveness in reducing tumor size (Dose Expansion) based on objective response rate criteria. It also examines the drugs' pharmacokinetics—their movement through the body.

How Is the Trial Designed?

Group I: Module 3-Combo Therapy Experimental Treatment 3 Interventions

REGN4336 + REGN5678

Group II: Module 2-Combo Therapy Experimental Treatment 3 Interventions

REGN4336 + Cemiplimab

Group III: Module 1- Monotherapy Experimental Treatment 2 Interventions

REGN4336

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

Androgen deprivation therapy is the standard first-line treatment for advanced prostate cancer, but many patients eventually develop castration-resistant prostate cancer (CRPC), necessitating alternative treatments.

New hormonal agents like abiraterone and enzalutamide, along with the cancer vaccine Sipuleucel T, have been approved for CRPC, highlighting the need for personalized treatment strategies due to the disease's heterogeneity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel agents in the management of castration resistant prostate cancer. Chaturvedi, S., Garcia, JA.[2022]

The bispecific 5-alpha-reductase inhibitor LY320236 was well tolerated in a study of 51 patients with prostate cancer, with only a small number experiencing reversible severe side effects, indicating a favorable safety profile.

While LY320236 did not significantly alter testosterone or dihydrotestosterone levels, it led to a notable increase in estradiol levels and resulted in a 50% or greater decline in PSA levels in some patients, particularly those in the castration group, suggesting potential efficacy in managing prostate cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and clinical pharmacology of a type I and II, 5-alpha-reductase inhibitor (LY320236) in prostate cancer: elevation of estradiol as possible mechanism of action. Eisenberger, MA., Laufer, M., Vogelzang, NJ., et al.[2019]

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]

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]

Interleukin-6 promotes the expression of the androgen receptor splice variant AR-V7 in prostate cancer, which contributes to resistance against androgen receptor signaling inhibitors (ARSIs).

The combination treatment of the CD105-neutralizing antibody carotuximab with ARSIs showed disease stabilization in 4 out of 9 patients with ARSI-resistant prostate cancer, indicating a potential strategy to overcome resistance by downregulating AR-V7.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit. Smith, BN., Mishra, R., Billet, S., et al.[2023]

In a phase II study involving 69 patients with metastatic castration-resistant prostate cancer, the combination of sipuleucel-T with abiraterone acetate plus prednisone (AA + P) did not negatively affect the immune responses or the manufacturing of sipuleucel-T, indicating that these treatments can be safely administered together.

Both concurrent and sequential administration of AA + P showed significant immune activation, suggesting that sipuleucel-T retains its immunologic benefits even when combined with other therapies, and the combination was well tolerated without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Trial of Sipuleucel-T with Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer. Small, EJ., Lance, RS., Gardner, TA., et al.[2016]

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. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS295

Phase 1/2 study of REGN4336 alone or in combination ... Preclinically, nezastomig + subtherapeutic doses of REGN4336 showed similar efficacy and reduced cytokines compared with higher doses of ...

2. stanfordhealthcare.org stanfordhealthcare.org/trials/a/NCT05125016.html

A Trial to Find Out if REGN4336 is Safe and How Well it ... The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug) and effectiveness of REGN4336 alone, in combination ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33067297/

Protocol of a prospective, multicentre phase I study to ... To address the high medical need in castration-resistant prostate cancer (CRPC), we generated a novel PSMAxCD3 bispecific antibody termed CC-1.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2536

Updated results on the bispecific PSMAxCD3 antibody CC ... A rapid and profound decline of PSA levels with up to 62% reduction compared to baseline was documented in all but one of the heavily pretreated ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04104607

NCT04104607 | The Bispecific PSMAxCD3 Antibody CC-1 ... This trial is a first in human (FIH) study in patients with castration resistant metastatic prostate cancer (CRPC) after failure of third-line therapy.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS284

A phase 1/2 study of REGN4336, a PSMAxCD3 bispecific ... REGN4336 is a PSMAxCD3 bispecific antibody designed to facilitate T-cell–mediated killing of PSMA-expressing tumor cells.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04104607?term=AREA%5BBasicSearch%5D(castration%20resistant%20prostate%20cancer%20phase%203)&rank=8

The Bispecific PSMAxCD3 Antibody CC-1 in Patients with ... This trial is a first in human (FIH) study in patients with castration resistant metastatic prostate cancer (CRPC) after failure of third-line therapy ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT406940

Clinical development of the bispecific PSMAxCD3 antibody ... We report on the clinical development of CC-1, a PSMAxCD3 bsAb, in an IgG-based format that induces fully target cell-restricted T cell activity.