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

Trial Summary

What is the purpose of this trial?

This trial is testing a new cancer drug called REGN4336, alone or with other drugs, to see if it is safe and effective. It aims to help the immune system attack cancer cells. The study focuses on finding the right dose and understanding side effects.

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.

What data supports the effectiveness of the drug REGN4336 + Cemiplimab for prostate cancer?

The research highlights that bispecific antibodies like the PSMAxCD3 antibody can target prostate-specific membrane antigens on cancer cells, potentially offering a dual anticancer effect. However, while bispecific antibodies are promising in theory, they have not yet been successful in treating solid tumors like prostate cancer. ^{1 2 3 4 5}

What makes the drug REGN4336 + Cemiplimab unique for prostate cancer?

REGN4336 + Cemiplimab is unique because it combines a bispecific antibody that targets prostate-specific membrane antigen (PSMA) on cancer cells with an immune checkpoint inhibitor, potentially enhancing the immune system's ability to attack prostate cancer cells. This approach is novel as it leverages both targeted and immune-based strategies, which are not yet standard for prostate cancer treatment. ^{1 2 5 6 7}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Targeted therapies for prostate cancer. [2019]

4. India pubmed.ncbi.nlm.nih.gov

Novel agents in the management of castration resistant prostate cancer. [2022]

5. United States 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. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit. [2023]

7. United States 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. [2019]