REGN5678 Before Surgery for High-Risk Prostate Cancer

Recruiting at 1 trial location

Overseen By Sumit Subudhi, MD, PHD

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Hormone therapy, Corticosteroids

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: 6 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, REGN5678 (a PSMAxCD28 costimulatory bispecific antibody), for safety and effectiveness in men with high-risk prostate cancer. Researchers aim to evaluate how this drug performs when administered before prostate cancer surgery. The trial seeks men diagnosed with aggressive prostate cancer who have not yet received treatment. Participants will receive the drug weekly for six weeks and will be closely monitored for side effects. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain treatments like systemic corticosteroids or other immunosuppressive drugs within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that REGN5678 is likely to be safe for humans?

Research has shown that REGN5678 is being tested for its safety and effectiveness in treating prostate cancer. In ongoing studies, most participants have tolerated REGN5678 well, though some have experienced side effects, which is common with new treatments. These side effects have varied, but medical professionals closely monitor them.

The treatment aims to help the body's immune system better target cancer cells. Since REGN5678 remains in the early stages of human testing, researchers are actively collecting data to understand its safety. They study how the drug affects the body and what side effects might occur.

Prospective trial participants should discuss potential risks and benefits with their healthcare provider. Providers can offer detailed information about what to expect when participating in the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Unlike standard treatments for high-risk prostate cancer, which often include surgery, radiation, and hormone therapy, REGN5678 introduces a novel approach by targeting a specific protein on cancer cells called PSMA. This treatment is unique because it combines an anti-PSMA antibody with CD28, a molecule that helps stimulate the immune system. This dual-action mechanism not only aims to directly attack the cancer cells but also enhances the body's immune response, potentially leading to more effective outcomes. Researchers are excited about REGN5678 because it represents a new frontier in cancer therapy by leveraging the immune system in a targeted manner, offering hope for better management of high-risk prostate cancer.

What evidence suggests that REGN5678 might be an effective treatment for high-risk prostate cancer?

Research has shown that REGN5678, which participants in this trial will receive, may help treat prostate cancer by enhancing the immune system's ability to fight cancer cells. This drug is a special type of antibody that links immune cells, called T cells, to prostate cancer cells, boosting the immune system's effectiveness against the cancer. Early studies found that higher doses of REGN5678 increased anti-tumor activity in just six weeks. Although this treatment is still under development, these early results suggest that REGN5678 could be effective for patients with high-risk prostate cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Sumit K. Subudhi, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with high-risk, localized prostate cancer that hasn't spread and is operable. They must have a specific Gleason score from recent biopsies, good organ function, no prior prostate cancer treatments, and an ECOG performance status of 0 or 1. Participants need to agree to use condoms during the study and for three months after.

Inclusion Criteria

Platelet count ≥100 x 109 /L

ALT ≤2.5 x ULN

Alkaline Phosphatase (ALP) ≤2.5 x ULN

Exclusion Criteria

I have myocarditis.

I have inflammation or significant fluid around my heart.

I have not had major surgery within the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REGN5678 weekly for 6 weeks, with initial administration over 2 hours and subsequent doses over 30-90 minutes

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• REGN5678

Trial Overview The trial tests REGN5678 (an experimental drug) in combination with Piflufolastat F18 before patients undergo surgery for prostate cancer. The goal is to assess the safety and effects of REGN5678 on men preparing for radical prostatectomy.

How Is the Trial Designed?

Group I: REGN5678 (anti-PSMAxCD28) Experimental Treatment 2 Interventions

Participants will receive REGN5678 by vein over about 2 hours the first time you receive it. Participants will be admitted to the hospital, where participants will be monitored for side effects. Other doses may be given over 30-90 minutes depending on how you handle the dose. Participants will receive REGN5678 weekly for 6 weeks.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Prostate cancer has a challenging immunosuppressive environment, making it difficult to treat with traditional immunotherapy; currently, sipuleucel-T is the only FDA-approved immunotherapy specifically for prostate cancer, effective mainly for select patients with indolent metastatic castration-resistant prostate cancer.

Future strategies in immuno-oncology for prostate cancer may involve innovative approaches like bispecific antibodies and CAR-T cells targeting specific markers on tumor cells, which could improve patient outcomes by overcoming the immune barriers present in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. Wong, RL., Yu, EY.[2022]

TSAxCD28 bispecific antibodies can enhance the effectiveness of anti-PD-1 therapy, enabling immune responses and long-term memory against tumors that typically do not respond to PD-1 blockers, as demonstrated in preclinical models.

These bispecifics show minimal toxicity compared to other T cell activators, making them a promising and safe addition to cancer immunotherapy regimens, potentially improving outcomes for patients with resistant tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Waite, JC., Wang, B., Haber, L., et al.[2021]

A new bispecific antibody targeting both PSMA (a prostate cancer marker) and CD3 (a T cell marker) shows promise in inhibiting tumor growth in preclinical models, particularly in mice with low tumor burdens.

Combining this PSMAxCD3 antibody with 4-1BB costimulation significantly enhances T cell activation and proliferation, improving efficacy against larger tumors and promoting long-lasting antitumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PSMA-Targeting CD3 Bispecific Antibody Induces Antitumor Responses that Are Enhanced by 4-1BB Costimulation. Chiu, D., Tavaré, R., Haber, L., 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]

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 CCW702 effectively targets metastatic castration-resistant prostate cancer (mCRPC) by combining T cell recruitment with specificity for prostate-specific membrane antigen, showing potent in vitro cytotoxicity and improved stability compared to previous formats.

In animal studies, CCW702 demonstrated significant tumor elimination with just three doses and was well tolerated in cynomolgus monkeys, supporting its potential for a weekly dosing regimen in upcoming human trials for patients with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand. Lee, SC., Ma, JSY., Kim, MS., et al.[2022]

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]

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 ... REGN5678 is a first-in-class, full-length anti-PSMAxCD28 bispecific costimulatory antibody designed to target prostate cancer cells and enhance T-cell ...

2. investor.regeneron.com investor.regeneron.com/node/26851/pdf

Novel Costimulatory Bispecific Antibody ... REGN5678 is one of Regeneron's three clinical-stage costimulatory bispecifics, all of which are designed to bridge T cells to cancer cells and ...

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. 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- ...

5. researchgate.net researchgate.net/publication/369254409_Preliminary_results_from_a_phase_12_study_of_co-stimulatory_bispecific_PSMAxCD28_antibody_REGN5678_in_patients_pts_with_metastatic_castration-resistant_prostate_cancer_mCRPC

Preliminary results from a phase 1/2 study of co-stimulatory ... Preliminary results from a phase 1/2 study of co-stimulatory bispecific PSMAxCD28 antibody REGN5678 in patients (pts) with metastatic castration ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2021.39.6_suppl.TPS174

A phase I/II study of REGN5678 (Anti-PSMAxCD28 ... Methods: This is an open label, Phase I/II, first-in-human study evaluating safety, tolerability, pharmacokinetics (PK), and anti-tumor activity ...