Neoadjuvant Enoblituzumab for Prostate Cancer

(HEAT Trial)

Recruiting at 4 trial locations

Overseen By Carolyn Chapman GU oncology

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: Other prostate cancers, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: 8

Duration: 12 weeks

219 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the efficacy, anti-tumor effect, and immunogenicity of neoadjuvant enoblituzumab given before radical prostatectomy. Patients will be randomized to enoblituzumab for a total of 12 weeks beginning 84 days before radical prostatectomy or standard of care arms.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use systemic corticosteroids or other hormonal therapies during the trial.

What data supports the effectiveness of the drug Enoblituzumab for prostate cancer?

In a phase 2 trial, Enoblituzumab, which targets a protein called B7-H3 found in prostate cancer, showed potential effectiveness with 66% of patients having undetectable prostate-specific antigen (PSA) levels one year after surgery, indicating a promising anti-tumor activity. ^{1 2 3 4 5}

Is Enoblituzumab generally safe for humans?

In a study with prostate cancer patients, Enoblituzumab was found to be generally safe, with no unexpected complications and only 12% of patients experiencing moderate side effects, while no severe side effects were reported. ^{1 6 7 8 9}

How does the drug enoblituzumab differ from other treatments for prostate cancer?

Enoblituzumab is unique because it targets B7-H3, a protein highly expressed in prostate cancer, and works by enhancing the immune system's ability to attack cancer cells. This approach is different from traditional treatments that may not specifically target this protein, making enoblituzumab a novel option for prostate cancer therapy. ^{1 7 10 11 12}

Research Team

Eugene Shenderov

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

Men with high-risk localized prostate cancer that hasn't spread to lymph nodes, bones, or organs. Eligible participants must have a specific type of tumor (adenocarcinoma), certain levels of blood cells and organ function, agree to use barrier contraception, and be able to follow study requirements. Those who've had prior treatments for prostate cancer or have other health conditions like autoimmune diseases are excluded.

Inclusion Criteria

AST <3 × ULN

WBC >3,000 cells/mm3

Serum bilirubin <1.5 × ULN

Exclusion Criteria

My prostate cancer is not the usual type.

My scans show cancer has spread to my lymph nodes or other parts.

I have not had cancer in the last 3 years, except for skin or superficial bladder cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive neoadjuvant Enoblituzumab 15mg/kg IV every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84

12 weeks

6 visits (in-person)

Post-Treatment Evaluation

Prostate glands are harvested at radical prostatectomy, and prostate tissue is examined for pathologic response and secondary pharmacodynamic/immunologic endpoints

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.

3 years

Multiple visits (in-person)

Treatment Details

Interventions

• Enoblituzumab
• Standard of Care

Trial Overview The trial is testing the effectiveness of Enoblituzumab given before surgery compared to standard care in men with high-risk prostate cancer. Participants will either receive Enoblituzumab for 12 weeks before their scheduled radical prostatectomy or undergo the usual treatment without this drug.

Participant Groups

Group I: Enoblituzumab Experimental Treatment 1 Intervention

Men with localized intermediate and high-risk prostate cancer will be given neoadjuvant Enoblituzumab 15mg/kg IV every 2 weeks for 12 weeks, followed by a radical prostatectomy on day 84, with follow-up visits 30 days, 90 days, 6 months, and 9 months post-prostatectomy. PSA values will be tracked for 3 years post-prostatectomy.

Group II: Standard of Care Active Control 1 Intervention

Patients will undergo standard of care radical prostatectomy within 4-8 weeks of randomization.

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+

Findings from Research

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]

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

In a clinical trial involving eight high-risk prostate cancer patients, neoadjuvant treatment with rituximab significantly reduced the density of CD20+ B-cells and CD3+ T-cells in tumor regions compared to control samples, indicating a potential immunotherapeutic effect.

Rituximab was well-tolerated by patients and successfully modified the immune environment of prostate tumors, particularly in tertiary lymphoid structures, suggesting a complex interaction between B-cells and T-cells in prostate cancer that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant rituximab modulates the tumor immune environment in patients with high risk prostate cancer. Ryan, ST., Zhang, J., Burner, DN., et al.[2022]

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]

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]

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]

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 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]

Nimotuzumab, a humanized IgG1 monoclonal antibody targeting the epidermal growth factor receptor, has been evaluated for its potential in treating prostate cancer with bone metastases, which typically indicate a poor prognosis.

Immunoscintigraphic imaging demonstrated the ability of Tc-labeled nimotuzumab to visualize bone metastases expressing the receptor, suggesting its utility in identifying affected areas for targeted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoscintigraphy With 99mTc-Nimotuzumab for Planning Immunotherapy in Patients With Bone Metastases Due to Prostate Cancer. Quián, YP., Crombet, T., Batista, JF., et al.[2018]

Monoclonal antibodies (MAbs) are emerging as a promising treatment option for prostate cancer (PCa), particularly due to the disease's characteristics that allow for targeted therapy without harming normal prostate tissue.

There is ongoing development of MAbs targeting both established and novel cancer-related proteins, with many products currently in preclinical and clinical trials, highlighting the potential for new therapies in advanced PCa where effective treatments are currently lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy for prostate cancer. Jakobovits, A.[2007]

In three cases of metastatic castration-resistant prostate cancer (mCRPC), patients showed significant responses to anti-PD-1 immunotherapy after being treated with bipolar androgen therapy (BAT) and enzalutamide, suggesting a potential strategy for enhancing immunotherapy effectiveness.

Two of the patients had inactivating mutations in HR DNA repair genes (BRCA2, ATM), indicating that specific genetic profiles may influence the success of immune checkpoint blockade in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extreme responses to immune checkpoint blockade following bipolar androgen therapy and enzalutamide in patients with metastatic castration resistant prostate cancer. Markowski, MC., Shenderov, E., Eisenberger, MA., et al.[2021]

References

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

Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial. [2023]

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

Evaluation of B7-H3 expression as a biomarker of biochemical recurrence after salvage radiation therapy for recurrent prostate cancer. [2019]

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

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]

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

Neoadjuvant rituximab modulates the tumor immune environment in patients with high risk prostate cancer. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis. [2021]

7. United States 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. [2023]

8. England 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. [2022]

9. United States 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. [2020]

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

Immunoscintigraphy With 99mTc-Nimotuzumab for Planning Immunotherapy in Patients With Bone Metastases Due to Prostate Cancer. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy for prostate cancer. [2007]

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

Extreme responses to immune checkpoint blockade following bipolar androgen therapy and enzalutamide in patients with metastatic castration resistant prostate cancer. [2021]