REGN5678 +/- Cemiplimab for Prostate Cancer

Recruiting at26 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to determine the safety, tolerability (how your body reacts to the drug) and effectiveness (ability to treat your cancer) of REGN5678 alone, or in combination with cemiplimab. The study has 2 parts. The goal of Part 1 (dose escalation) is to determine a safe dose(s) of REGN5678 when it is given alone or in combination with cemiplimab. The goal of Part 2 (dose expansion) is to use the REGN5678 drug dose(s) found in Part 1 to see how well REGN5678 alone or in combination with cemiplimab works to shrink tumors. This study is looking at several other research questions, including: 1. Side effects that may be experienced by taking REGN5678 alone or in combination with cemiplimab 2. How REGN5678 alone or in combination with cemiplimab works in the body 3. How much REGN5678 and/or cemiplimab are present in the blood 4. To see if REGN5678 alone or in combination with cemiplimab works to reduce the size of the tumor by helping the immune system destroy the tumor

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.

What data supports the effectiveness of the drug REGN5678 +/- Cemiplimab for prostate cancer?

The bispecific PSMAxCD3 antibody CC-1, similar to REGN5678, has shown potential in targeting prostate cancer cells by binding to specific proteins on these cells, suggesting a possible dual anticancer effect. However, while immunotherapies have been successful in other cancers, they have largely been unsuccessful in prostate cancer, with sipuleucel-T being the only approved immunotherapy for this condition. ^{1 2 3 4 5}

How is the drug REGN5678 +/- Cemiplimab unique for prostate cancer treatment?

REGN5678 +/- 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 dual approach is different from traditional treatments and aims to address the high medical need in castration-resistant prostate cancer. ^{1 3 6 7 8}

Research Team

Clinical Trials Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cemiplimab (PD-1 Inhibitor)
• REGN5678 (Monoclonal Antibodies)

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.

Participant Groups

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

Participants will receive the REGN5678 presumptive RP2D(s)

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

Participants will receive REGN5678 monotherapy for presumptive recommended phase 2 dose(s) (presumptive RP2D) identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use.

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

Participants will receive the REGN5678 presumptive RP2D(s)

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

Participants will receive REGN5678 monotherapy for presumptive RP2D identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use.

Cemiplimab is already approved in Canada, Brazil for the following indications:

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]

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]

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]

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]

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 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]

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]

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. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Targeted therapies for prostate cancer. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Evolving Role of Immunotherapy in Metastatic Castration Refractory Prostate Cancer. [2021]

6. United States 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). [2022]

7. England 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Passive-specific immunotherapy with monoclonal antibodies for prostate cancer: A systematic review. [2021]