Enfortumab Vedotin for Prostate Cancer

(ENCORE Trial)

Overseen By Susan Sharry

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Utah

Must be taking: Androgen-deprivation therapy

Disqualifiers: Concurrent malignancy, Cardiovascular disease, HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 months

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies enfortumab vedotin, a new treatment for prostate cancer that has spread and resists standard hormone therapy. Researchers aim to evaluate the drug's effectiveness alone and potentially in combination with other cancer treatments. It targets men with hormone-resistant prostate cancer who have previously received certain cancer drugs. This trial provides a new option for those who have tried standard treatments but need alternatives. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a promising new option for patients seeking alternatives.

Will I have to stop taking my current medications?

The trial requires you to stop all previous cancer treatments (except for hormone therapy and bone loss prevention) 28 days before starting the study. If you're taking any prohibited medications, you'll need to stop them for a period of at least 5 half-lives or as advised by your doctor before beginning the trial.

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

Research has shown that enfortumab vedotin is generally safe to use. In previous studies with patients who had undergone multiple treatments for advanced prostate cancer, the drug demonstrated promising results. "Generally safe" means that most patients managed the side effects, which were not too severe.

The FDA has already approved enfortumab vedotin for treating other cancers, such as advanced bladder cancer, indicating it is usually well-tolerated. However, individual experiences may vary, so discussing possible side effects with the trial team is important. ^{1 2 3 4 5}

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

Researchers are excited about Enfortumab Vedotin for prostate cancer because it introduces a novel mechanism of action compared to standard treatments. Unlike traditional therapies that typically target hormone pathways, Enfortumab Vedotin is an antibody-drug conjugate designed to deliver chemotherapy directly to cancer cells by targeting a protein called Nectin-4. This targeted approach could potentially minimize damage to healthy cells and reduce side effects, making it a promising option for patients who have limited success with existing treatments.

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

Studies have shown that enfortumab vedotin, which participants in this trial will receive, shows promise for treating advanced prostate cancer that no longer responds to hormone therapy. In earlier research, 4.9% of patients experienced a complete response, with their cancer no longer detectable, while 35.8% had a partial response, with significant tumor shrinkage. Researchers found it safe for patients who had already tried several other treatments. Although enfortumab vedotin is more commonly used for a type of bladder cancer, these findings suggest it could also be effective for this type of prostate cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to castration and has worsened after hormone therapy. They must have had prior chemotherapy, maintain low testosterone levels, and have good organ function. Participants need to agree to effective contraception and not have HIV or hepatitis with detectable viral loads.

Inclusion Criteria

I have completed at least three cycles of docetaxel therapy.

My cancer has spread and cannot be removed by surgery.

I have recovered from previous treatment side effects, or they are minor and stable.

Exclusion Criteria

Known HIV infection with a detectable viral load at the time of screening. Note: Patients on effective antiretroviral therapy with an undetectable viral load at the time of screening are eligible for this trial.

I do not have serious heart conditions like recent heart attacks or severe heart failure.

The subject has an uncontrolled, significant intercurrent or recent illness that would preclude safe study participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Enfortumab will be administered in monotherapy on days 1, 8, and 15 as part of a 28-day cycle at 1.25 mg/kg up to 125 mg

12 months

3 visits per 28-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin

Trial Overview The trial is testing Enfortumab Vedotin alone or with other anti-cancer drugs in men whose prostate cancer has spread and doesn't respond to hormone treatment anymore. It's an open-label phase II study where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Treatment: all patients Experimental Treatment 1 Intervention

Enfortumab will be administered in monotherapy on days 1, 8, and 15 as part of a 28-day cycle at 1.25 mg/kg up to 125 mg.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

Enfortumab vedotin, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., et al.[2023]

Enfortumab vedotin-ejfv (EV) is an effective treatment option for adults with locally advanced or metastatic urothelial carcinoma who have already received PD-1/PD-L1 inhibitors and platinum-based chemotherapy, as it targets the Nectin-4 protein.

To maximize the benefits of EV therapy, it is crucial to educate patients and caregivers, monitor for adverse events, and intervene promptly to manage any side effects that may arise during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. Pace, A., Brower, B., Conway, D., et al.[2021]

In a subgroup analysis of 86 Japanese patients with locally advanced or metastatic urothelial carcinoma, enfortumab vedotin (EV) demonstrated a median overall survival of 15.18 months, significantly longer than the 10.55 months observed with standard chemotherapy.

EV also showed a higher confirmed overall response rate (34.4%) compared to standard chemotherapy (21.3%), while having a lower incidence of treatment-related adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Japanese subgroup analysis of EV-301: An open-label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma. Matsubara, N., Yonese, J., Kojima, T., et al.[2023]

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

Citations

1. urotoday.com urotoday.com/conference-highlights/asco-gu-2024/asco-gu-2024-prostate-cancer/149306-asco-gu-2024-enfortumab-vedotin-as-monotherapy-in-patients-with-metastatic-castration-resistant-prostate-cancer-results-of-stage-i-of-a-phase-2-trial.html

ASCO GU 2024: Enfortumab Vedotin as Monotherapy in ... Dr. Swami concluded that enfortumab vedotin shows promising efficacy and an acceptable safety profile in patients with heavily treated, refractory mCRPC.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605113/

Clinical Review - Enfortumab Vedotin (Padcev) - NCBI - NIH Totals of 4.9% and 35.8% of patients achieved a confirmed complete response (CR) and partial response (PR), respectively, in the enfortumab vedotin arm compared ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155876732400257X

Real-world Effectiveness of Single-Agent Enfortumab ... EV demonstrates efficacy in patients with mUC regardless of prior receipt of platinum-based chemotherapy and PD-1/L1 inhibitors or treatment line.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2035807

Enfortumab Vedotin in Previously Treated Advanced ... Enfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma.

5. padcevhcp.com padcevhcp.com/padcev-efficacy

Post-platinum, Post-PD-(L)1 PADCEV® Monotherapy Efficacy PADCEV significantly improved OS* vs chemotherapy 1 PADCEV reduced the risk of death by 30% vs chemotherapy (HR=0.70; 95% CI: 0.56, 0.89; P=0.0014)

6. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-press-releases/158093-pfizer-and-astellas-padcev-enfortumab-vedotin-ejfv-plus-keytruda-pembrolizumab-shows-long-term-efficacy-in-first-line-treatment-of-locally-advanced-or-metastatic-urothelial-cancer-la-muc.html

Pfizer and Astellas' PADCEV® (enfortumab vedotin-ejfv) ... Results showed enfortumab vedotin plus pembrolizumab reduced the risk of death by 49% versus chemotherapy (hazard ratio [HR] = 0.51, 95% ...

7. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.