REGN5678 + Cemiplimab for Prostate Cancer

Overseen By Bilal Siddiqui, MD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: LHRH agonist or antagonist

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 6

Duration: 9 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments: REGN5678 (an experimental treatment) and cemiplimab (a type of immunotherapy) for men with prostate cancer that has spread and continued to progress after standard treatments. The goal is to determine the best dose and evaluate the effectiveness of this combination. Eligible participants are men whose prostate cancer has not responded to at least two prior treatments, including therapy targeting male hormones. The trial involves regular clinic visits and specific requirements, such as using protection during sexual activity to prevent drug exposure. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like systemic corticosteroids or have received other systemic therapies recently. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of REGN5678 and cemiplimab has been studied to ensure safety. Earlier studies focused on identifying a safe dose when these drugs are used together. Initial results are promising, indicating that the combination may help fight cancer. However, the primary goal was to determine the safety of different doses.

In these studies, patients who received higher doses showed better results against tumors within six weeks. This suggests the treatment was effective at these doses, but researchers closely monitored safety to ensure patients could handle it.

Since this trial is in an early phase, researchers are still collecting information on how well people can tolerate the combination. This phase mainly ensures the treatment doesn't cause any severe harmful effects.

Overall, while early studies suggest the combination of REGN5678 and cemiplimab is promising, ongoing research will provide a clearer picture of its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of REGN5678 and cemiplimab for prostate cancer because it represents a novel approach to treatment. Unlike traditional options that typically focus on hormone therapy or chemotherapy, this combination leverages immunotherapy to target cancer cells. REGN5678 works by enhancing the body's immune response against prostate cancer cells, while cemiplimab, an anti-PD-1 antibody, blocks a protein that prevents the immune system from attacking cancer. This dual action has the potential to provide a more effective treatment by directly engaging and boosting the body's natural defenses against the cancer.

What evidence suggests that REGN5678 and cemiplimab could be effective for prostate cancer?

Research shows that combining the drugs REGN5678 and cemiplimab may help treat prostate cancer. Participants in this trial will receive this combination treatment. Early studies found that this combination can help the immune system attack and shrink tumors. Some patients receiving higher doses showed noticeable tumor reduction within just six weeks. This treatment aims to strengthen the body's natural defenses to fight cancer more effectively. Although still in the early stages, these findings suggest potential benefits for prostate cancer patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Bilal Siddiqui, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for men aged 18+ with advanced prostate cancer (mCRPC) that has worsened after at least two systemic therapies, including anti-androgen therapy. Participants must have adequate organ function, no active infections like HIV or hepatitis, and an ECOG performance status of 0 or 1. They should not be in other trials, have certain other cancers or severe health conditions, and must agree to use contraception.

Inclusion Criteria

My prostate cancer has worsened after two treatments, including a newer hormone therapy.

My blood tests show normal hemoglobin, neutrophil, and platelet levels.

My kidney function is within the normal range.

Exclusion Criteria

Currently receiving treatment in another interventional study

Any medical, psychological or social condition that in the opinion of the investigator, would preclude participation in this study

Has participated in a study of an investigational drug within 4-weeks of first dose of study therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-In Phase

Participants receive three weekly doses of REGN5678

3 weeks

3 visits (in-person)

Treatment

Participants transition to every three-week dosing of REGN5678 and cemiplimab

9 months

Visits every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• REGN5678

Trial Overview The study tests REGN5678 combined with Cemiplimab in a phase Ib/II trial involving dose escalation and expansion. It's designed to see how well these drugs work together for patients who've already tried multiple treatments for mCRPC.

How Is the Trial Designed?

Group I: Treatment with REGN5678 Q3W IV + Cemiplimab Q3W IV Experimental Treatment 2 Interventions

Patients will receive three weekly doses of REGN5678 as part of a Lead-In Phase and thentransition to every three-week dosing of the combination of REGN5678 and cemiplimab (anti-PD-1).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

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 IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

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]

In a study of men with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T, a delayed PSA response was observed, with 19.9% of patients in the PROCEED registry showing a PSA50 response at a median of 5.5 months after treatment.

The median overall survival for patients in the PROCEED cohort was 49 months, suggesting that sipuleucel-T may provide a significant survival benefit despite low immediate response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry. Wei, XX., Kwak, L., Hamid, A., et al.[2022]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

The vaccine-based immunotherapy regimen PF-06753512 (PrCa VBIR) demonstrated a safety profile similar to other immune checkpoint inhibitor (ICI) combination trials, with common side effects including fatigue and immune-related thyroid dysfunction in 70.3% of patients.

In patients with biochemical recurrence (BCR), 25.7% achieved a significant decline in PSA levels, indicating modest antitumor activity, while the treatment successfully stimulated antigen-specific immune responses across all patient cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Autio, KA., Higano, CS., Nordquist, L., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.154

Preliminary results from a phase 1/2 study of co-stimulatory ... Conclusions: Preliminary data on REGN5678 plus cemiplimab in pts with mCRPC provide first evidence of clinical activity of a CD28 co-stimulatory ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03972657

NCT03972657 | A Trial to Find Out if REGN5678 ... 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. Official Title.

3. 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 ...

4. withpower.com withpower.com/trial/regn5678-cemiplimab-for-prostate-cancer-dda9a

REGN5678 + Cemiplimab for Prostate Cancer This combination could offer a novel way to treat prostate cancer by enhancing the body's immune response against the tumor. Show more.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20585142

Clinical Trials A Trial To Find Out If REGN5678 Is Safe And How Well It Works Alone Or In Combination With Cemiplimab For Adult Participants With Metastatic ...

6. meetings.asco.org meetings.asco.org/abstracts-presentations/194886

A phase I/II study of REGN5678 (Anti-PSMAxCD28 ... A phase I/II study of REGN5678 (Anti-PSMAxCD28, a costimulatory bispecific antibody) with cemiplimab (anti–PD-1) in patients with metastatic castration- ...