Enoblituzumab for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Hormonal therapy, Corticosteroids

Disqualifiers: Metastases, Autoimmune disease, Malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Enoblituzumab, an experimental treatment, to determine its safety and effectiveness in treating prostate cancer before surgery. The goal is to assess its impact on tumors and the immune system. Participants will receive the drug weekly for six weeks before their scheduled prostate surgery. Men with prostate cancer, scheduled for surgery at Johns Hopkins Hospital, and with at least two positive cancer spots in a biopsy may qualify for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use systemic corticosteroids or hormonal therapy for prostate cancer. If you are on these, you may need to stop or switch medications.

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

Research has shown that enoblituzumab is generally well-tolerated by patients with prostate cancer. In studies of this treatment, patients experienced positive safety outcomes. Most side effects were mild and manageable, such as fatigue or mild reactions during intravenous administration.

More detailed studies found that enoblituzumab was effective against prostate cancer while maintaining a good safety profile. This indicates the treatment worked against the cancer without causing many serious issues for patients.

The treatment is currently in Phase 2 trials, providing a fair amount of safety information. Phase 2 trials typically focus on assessing the treatment's safety and efficacy. Since enoblituzumab is in this phase, there is a reasonable level of confidence in its safety for humans. ^{1 2 3 4 5}

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

Enoblituzumab is unique because it targets a specific protein called B7-H3, which is often found in high levels on cancer cells, including those in prostate cancer. Unlike standard treatments like surgery, radiation, or hormone therapy, which can have broad effects on the body, Enoblituzumab zeroes in on this protein, potentially leading to more precise cancer cell targeting with fewer side effects. Researchers are excited because this targeted approach might improve outcomes for patients with intermediate and high-risk prostate cancer by effectively reducing cancer cells before surgery.

What evidence suggests that Enoblituzumab might be an effective treatment for prostate cancer?

Studies have shown that enoblituzumab, a treatment targeting the protein B7-H3, can help fight prostate cancer. This protein often appears in large amounts in prostate cancer cells. By focusing on B7-H3, enoblituzumab may enable the immune system to attack cancer cells more effectively. Research indicates that enoblituzumab has produced promising results in shrinking tumors in men with localized prostate cancer. It has also proven safe, with patients tolerating the treatment well. These findings suggest that enoblituzumab could serve as a potential treatment option for prostate cancer. Participants in this trial will receive enoblituzumab as part of their treatment regimen. ^{1 2 3 4 5}

Who Is on the Research Team?

Eugene Shenderov, MD, PhD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

Men over 18 with intermediate/high-risk localized prostate cancer (stage T1c-T3b, N0, M0) can join. They must have a scheduled radical prostatectomy at Johns Hopkins Hospital, good physical health and organ function, and agree to use barrier contraception from the first dose until surgery. Excluded are those who've had prior treatments for prostate cancer or other cancers in the last 3 years (except certain skin/bladder cancers), autoimmune diseases needing immunosuppression, major illnesses, or known HIV/hepatitis B/C.

Inclusion Criteria

My prostate cancer is confirmed and has not spread to lymph nodes, bones, or other organs.

I am scheduled for a major prostate surgery at Johns Hopkins Hospital.

WBC >3,000 cells/mm3

Exclusion Criteria

You have previously taken experimental drugs for prostate cancer.

I haven't taken any systemic corticosteroids in the last 4 weeks.

I have received treatments like radiation or hormone therapy for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Enoblituzumab 15mg/kg IV weekly for 6 weeks

6 weeks

6 visits (in-person)

Surgery

Radical prostatectomy is performed 14 days after the last dose of Enoblituzumab

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, with PSA evaluations every 3 months during year 1 and every 6 months during years 2-3

3 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Enoblituzumab

Trial Overview

The trial is testing Enoblituzumab's safety and effectiveness when given before surgical removal of the prostate. Participants will receive six weekly doses starting about seven weeks before their surgery to see if it helps reduce tumor size and affects immune response.

How Is the Trial Designed?

Group I: Enoblituzumab Experimental Treatment 1 Intervention

Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV weekly for 6 weeks followed by radical prostatectomy on day 50, with follow-up visits 30 days and 90 days post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

MacroGenics

Industry Sponsor

Trials

51

Recruited

5,400+

Published Research Related to This Trial

Tislelizumab, a PD-1 inhibitor, significantly improved the overall response rate (ORR) and disease control rate (DCR) in patients with malignant solid tumors, with odds ratios of 2.59 and 1.78, respectively, based on a meta-analysis of seven phase III trials involving 3478 participants.

The treatment also demonstrated improved overall survival (OS) and progression-free survival (PFS), with hazard ratios of 0.71 and 0.68, indicating that tislelizumab is an effective option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tislelizumab for malignant solid tumor: a systematic review and meta-analysis of phase III randomized trials. Abushanab, AK., Mustafa, MT., Mousa, MT., et al.[2023]

In a phase II study involving 144 patients with castration-resistant prostate cancer, the combination of rilotumumab and mitoxantrone/prednisone did not significantly improve overall survival compared to the control group, with median survival times of 12.2 months versus 11.1 months.

Rilotumumab was generally well tolerated, although it was associated with a higher incidence of peripheral edema (24% vs. 8% in the control group), and high tumor MET expression may indicate a poorer prognosis for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted MET inhibition in castration-resistant prostate cancer: a randomized phase II study and biomarker analysis with rilotumumab plus mitoxantrone and prednisone. Ryan, CJ., Rosenthal, M., Ng, S., et al.[2020]

In a phase I/II study involving 133 patients, the combination of enoblituzumab (an anti-B7-H3 antibody) and pembrolizumab (a PD-1 inhibitor) showed promising antitumor activity, with objective response rates of 33.3% in HNSCC and 35.7% in NSCLC patients who had not previously received checkpoint inhibitors.

The treatment was generally well-tolerated, with a maximum tolerated dose not reached, although 87.2% of patients experienced treatment-related adverse events, including one treatment-related death due to pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial. Aggarwal, C., Prawira, A., Antonia, S., et al.[2022]

In a phase 2 trial involving 32 men with localized prostate cancer, the B7-H3-targeting antibody enoblituzumab was found to be generally safe, with only 12% of patients experiencing grade 3 adverse events and no grade 4 events reported.

One year after prostate surgery, 66% of patients had undetectable prostate-specific antigen (PSA) levels, suggesting that enoblituzumab may have promising anti-tumor activity in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial. Shenderov, E., De Marzo, AM., Lotan, TL., et al.[2023]

In a study of 148 men who underwent salvage radiation therapy for recurrent prostate cancer, higher levels of B7-H3 expression in primary tumors were linked to an increased risk of biochemical recurrence (BCR), with marked staining showing a relative risk of 4.40.

This research suggests that B7-H3 could be a potential target for future adjuvant therapies, as it may help predict which patients are at higher risk for recurrence after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of B7-H3 expression as a biomarker of biochemical recurrence after salvage radiation therapy for recurrent prostate cancer. Parker, AS., Heckman, MG., Sheinin, Y., et al.[2019]

In a phase 1 study involving 39 patients with metastatic castration-resistant prostate cancer, the bispecific antibody JNJ-63898081 (JNJ-081) showed potential by causing transient decreases in PSA levels, indicating some antitumor activity.

Cytokine release syndrome (CRS) and infusion-related reactions (IRR) were observed but could be reduced with subcutaneous dosing and step-up priming, suggesting a safer administration method for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Study of Safety and Preliminary Clinical Activity of JNJ-63898081, a PSMA and CD3 Bispecific Antibody, for Metastatic Castration-Resistant Prostate Cancer. Lim, EA., Schweizer, MT., Chi, KN., et al.[2023]

Higher levels of B7-H3 mRNA expression in prostate cancer patients are associated with more aggressive disease characteristics, such as higher Gleason scores and advanced tumor stages, indicating its potential as a prognostic marker.

B7-H3 expression is influenced by androgen signaling, as shown by its correlation with androgen receptor activity, suggesting that targeting B7-H3 could be a therapeutic strategy in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis. Benzon, B., Zhao, SG., Haffner, MC., et al.[2021]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10921422/

Neoadjuvant enoblituzumab in localized prostate cancer

We hypothesized that B7-H3-targeted antibodies with ADCC activity might improve outcomes in men with high-risk prostate cancer undergoing ...

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This multicenter, phase I, cohort expansion study was performed to characterize the safety, pharmacokinetics, pharmacodynamics, immunogenicity, ...

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Study design. This is a single-center, single arm, open-label pilot study evaluating the safety, anti- tumor effect, and immunogenicity of ...

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Targeting B7-H3 in prostate cancer: Phase 2 trial ...

In this neoadjuvant trial, inhibition of B7-H3 with enoblituzumab demonstrated favorable safety and encouraging activity in localized PCa patients.

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urotoday.com

urotoday.com/conference-highlights/esmo-2021/esmo-2021-prostate-cancer/132142-esmo-2021-phase-2-neoadjuvant-trial-of-the-anti-b7-h3-antibody-enoblituzumab-in-men-with-localized-prostate-cancer-safety-efficacy-and-immune-correlates.html

ESMO 2021: Phase 2 Neoadjuvant Trial of the anti–B7-H3 ...

The study sought to evaluate the safety, anti-tumor efficacy, and immunogenicity of enoblituzumab when given prior to prostatectomy.