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

Trial Summary

What is the purpose of this trial?

To learn about the safety and effects of a drug called REGN5678 when it is given to patients with high-risk prostate cancer.

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.

What data supports the effectiveness of the drug REGN5678 for high-risk prostate cancer?

Research on similar treatments shows that bispecific antibodies, like those targeting PSMA and CD28, can enhance the body's immune response against prostate cancer cells. These antibodies have shown promise in early trials by activating immune cells to attack cancer cells, potentially improving outcomes for patients with prostate cancer. ^{1 2 3 4 5}

Is REGN5678 safe for humans?

REGN5678, a type of bispecific antibody, has shown little or no toxicity in preclinical studies with mice and primates, suggesting it may be well-tolerated in humans. ^{1 2 4 5 6}

What makes the drug REGN5678 unique for treating high-risk prostate cancer?

REGN5678 is unique because it is a bispecific antibody that targets both the prostate-specific membrane antigen (PSMA) on cancer cells and the CD28 receptor on T cells, enhancing the immune system's ability to attack the cancer. This dual targeting approach is different from traditional treatments and aims to improve the immune response against prostate cancer. ^{1 2 4 5 7}

Research Team

Sumit K. Subudhi, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

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

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. [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

A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand. [2022]

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

A PSMA-Targeting CD3 Bispecific Antibody Induces Antitumor Responses that Are Enhanced by 4-1BB Costimulation. [2021]

5. 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]

6. 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]

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

Refining Immuno-Oncology Approaches in Metastatic Prostate Cancer: Transcending Current Limitations. [2022]