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

Trial Summary

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.

What data supports the effectiveness of the drug Enfortumab Vedotin for prostate cancer?

Enfortumab Vedotin has been shown to be effective in treating urothelial cancer, with a 44% response rate in patients who had previously received other treatments. While this data is specific to urothelial cancer, it suggests potential effectiveness in other cancers, like prostate cancer, due to its mechanism of targeting cancer cells. ^{1 2 3 4 5}

What safety information is available for Enfortumab Vedotin?

Enfortumab Vedotin, also known as Padcev, has been associated with several safety concerns, including high blood sugar (hyperglycemia), nerve damage (peripheral neuropathy), eye problems, skin reactions, and risks to unborn babies. Serious skin reactions occurred in up to 47% of patients, and severe side effects were reported in 73% of patients in some studies. ^{1 2 3 4 6}

How is the drug Enfortumab Vedotin different from other prostate cancer treatments?

Enfortumab Vedotin is unique because it is an antibody-drug conjugate that targets a protein called Nectin-4, which is not a standard approach for prostate cancer. It has been primarily used for urothelial cancer, showing effectiveness in patients who have already received other treatments, but its application in prostate cancer is novel. ^{1 2 4 5 6}

What is the purpose of this trial?

This trial is testing enfortumab, a drug that targets and kills cancer cells, in patients with prostate cancer that has spread and does not respond to hormone treatments. The goal is to see how well enfortumab works in these patients.

Research Team

Umang Swami, MD

Principal Investigator

Huntsman Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 (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]

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-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]

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]

References

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

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

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

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

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

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

4. United States 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. [2023]

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

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. [2023]