Enfortumab Vedotin for Penile Cancer

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Antimicrobials, Investigational agents

Disqualifiers: Uncontrolled diabetes, CNS metastases, 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: 4

Duration: Varies (until disease progression or unacceptable toxicity)

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether enfortumab vedotin, an innovative cancer treatment, can help patients with squamous cell carcinoma of the penis that has spread or cannot be surgically removed. Enfortumab vedotin targets cancer cells by attaching to a specific protein on the tumor and delivering a cancer-fighting drug directly to them. Patients who have previously tried other treatments or have metastatic or inoperable squamous cell penile cancer may be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that enfortumab vedotin was well-tolerated in past trials for various cancers. In studies involving patients with advanced bladder cancer, the treatment was generally safe, though some experienced side effects.

Another study used enfortumab vedotin with pembrolizumab for bladder cancer patients unable to take certain chemotherapy drugs. The treatment proved effective, and patients generally tolerated it well.

Although these studies do not specifically address penile cancer, they suggest that enfortumab vedotin can be safe for individuals with advanced cancers. Discuss any concerns with the trial team to understand potential side effects. ^{1 2 3 4 5}

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

Researchers are excited about enfortumab vedotin for penile cancer because it offers a novel approach compared to current treatment options, which typically include surgery, radiation, or standard chemotherapy. Enfortumab vedotin is an antibody-drug conjugate that targets a protein called Nectin-4, commonly found on cancer cells, delivering chemotherapy directly to the tumor while sparing healthy cells. This targeted mechanism could potentially increase effectiveness and reduce side effects compared to traditional chemotherapy. By directly attacking cancer cells, enfortumab vedotin aims to improve outcomes for patients with this rare and challenging cancer.

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

Research has shown that enfortumab vedotin, the treatment under study in this trial, can be effective for certain cancers, such as bladder cancer, and shows promise for penile cancer. This treatment targets a protein called nectin-4, found on many cancer cells, and delivers a cancer-fighting drug directly to them. Early results suggest that this targeted method can slow or stop the growth of cancer cells. In other cancer types, enfortumab vedotin has helped 44% of patients by shrinking or eliminating their tumors. Although data for penile cancer is limited, a case report has shown a positive response in this type of cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Lance C. Pagliaro

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with penile squamous cell carcinoma that has spread or can't be surgically removed. Participants may have had previous cancer treatments, must have measurable disease, and good organ function. They should not have certain other cancers, uncontrolled illnesses, severe neuropathy, active infections or hepatitis B/C, known drug allergies, or untreated brain metastases.

Inclusion Criteria

I have PSCC that cannot be removed by surgery or has spread.

I cannot have surgery for my skin cancer due to health issues or because it's too advanced, or I chose not to.

My kidney function, measured by GFR or creatinine clearance, is adequate.

Exclusion Criteria

Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile)

My condition is a specific type of penile cancer called pure verrucous carcinoma.

My diabetes has been under control for the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle. Treatment continues in the absence of disease progression or unacceptable toxicity.

Varies (until disease progression or unacceptable toxicity)

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days post-treatment, then every 3 months until disease progression, followed by every 6 months for up to 5 years.

Up to 5 years

1 visit at 30 days, then every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Enfortumab Vedotin

Trial Overview The trial tests enfortumab vedotin's effectiveness on advanced penile cancer. It's a phase II study where the drug—a monoclonal antibody linked to an anti-cancer agent—targets tumor cells by attaching to nectin-4 protein and delivering a toxin to kill them.

How Is the Trial Designed?

Group I: Treatment (Enfortumab vedotin) Experimental Treatment 3 Interventions

Patients receive enfortumab vedotin IV over 30 minutes on days 1,8 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI throughout the study.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

In a study involving 11 patients with metastatic penile squamous cell carcinoma who had failed previous chemotherapy, panitumumab demonstrated activity with a clinical benefit rate of 45.5%, including complete and partial remissions in some patients.

The treatment was generally safe, with manageable side effects, although one patient experienced significant skin toxicity leading to treatment discontinuation; median overall survival was 9.5 months, suggesting potential for further exploration in earlier treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab Treatment for Advanced Penile Squamous Cell Carcinoma When Surgery and Chemotherapy Have Failed. Necchi, A., Giannatempo, P., Lo Vullo, S., et al.[2022]

A case of metastatic penile squamous cell carcinoma showed significant improvement in symptoms and radiographic results after treatment with the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV), highlighting its potential efficacy in a setting with limited treatment options.

This case supports the exploration of antibody-drug conjugates like EV for treating advanced penile squamous cell carcinoma, emphasizing the need for further studies to establish effective therapies for this rare disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin. Fahey, CC., Nebhan, CA., York, S., et al.[2023]

The combination of nimotuzumab, an anti-EGFR monoclonal antibody, with chemotherapy led to a partial response in a 44-year-old patient with penile squamous cell carcinoma (SCC) and metastasis, indicating potential efficacy of this treatment approach.

This study highlights the promising role of targeting EGFR in penile SCC, supported by previous findings that suggested benefits of anti-EGFR therapies in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy. Men, HT., Gou, HF., Qiu, M., et al.[2022]

In a study of 92 patients with locally advanced or metastatic penile squamous cell carcinoma, immune checkpoint inhibitors showed an overall survival of 9.8 months and a progression-free survival of 3.2 months, indicating potential efficacy in this challenging cancer type.

The objective response rate was 13% overall, but higher at 35% for patients with lymph node-only metastases, suggesting that certain patient subgroups may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors. El Zarif, T., Nassar, AH., Pond, GR., et al.[2023]

In a study of 24 patients with advanced penile or scrotal cancer, EGFR-targeted therapy, particularly cetuximab, demonstrated antitumor activity, with a median overall survival of 29.6 weeks and a time-to-disease-progression of 11.3 weeks.

Cetuximab, often used with cytotoxic drugs, showed a partial response rate of 23.5%, even in patients with chemotherapy-resistant tumors, suggesting it may enhance the effectiveness of cisplatin-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis. Carthon, BC., Ng, CS., Pettaway, CA., et al.[2022]

In a retrospective study of 9 patients with penile squamous cell carcinoma, three patients treated with the immune checkpoint inhibitor cemiplimab achieved nearly complete responses after just a few cycles, highlighting its potential efficacy as a first-line treatment.

One patient experienced cerebral arteritis during treatment but successfully managed it with high-dose steroids, allowing continued treatment with cemiplimab without further toxicity, suggesting a favorable safety profile for this immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience. Rouvinov, K., Mazor, G., Kozlener, E., et al.[2023]

Vinflunine demonstrated a clinical benefit rate of 45.5% in patients with inoperable squamous carcinoma of the penis, exceeding the pre-specified threshold for efficacy in a trial involving 25 patients.

While vinflunine showed promising activity, 68% of patients experienced significant adverse events, indicating that while it is a potential treatment option, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis. Nicholson, S., Tovey, H., Elliott, T., et al.[2022]

In a study of 47 patients with advanced penile squamous cell carcinoma, the T-PF chemotherapy regimen showed a 36.8% disease-free survival rate after neoadjuvant treatment compared to only 7.1% after adjuvant treatment, suggesting that neoadjuvant therapy may be more effective.

The T-PF regimen was generally well tolerated, with neutropenia being the most common severe side effect (25.5%), indicating that while the treatment can be effective, careful consideration is needed for patients with resectable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Combination of Cisplatin and 5-Fluorouracil With a Taxane in Patients Who Underwent Lymph Node Dissection for Nodal Metastases From Squamous Cell Carcinoma of the Penis: Treatment Outcome and Survival Analyses in Neoadjuvant and Adjuvant Settings. Nicolai, N., Sangalli, LM., Necchi, A., et al.[2018]

Penile cancer, primarily squamous cell carcinoma, is often linked to HPV in 30-40% of cases, and the prognosis for advanced stages is poor, with overall survival rates between 13.9 to 17.1 months.

Current first-line treatments involve platinum and taxane-based chemotherapy, but there is a need for new strategies due to limited efficacy of subsequent treatments and the frequent expression of PD-L1 in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic treatment of locally advanced or metastatic penile cancer]. Gassian, N., Frontczak, A., El Kaddissi, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10671469/

Metastatic Penile Squamous Cell Carcinoma Responsive ... Here, we present a case of metastatic penile squamous cell carcinoma with response to the Nectin-4 inhibitor enfortumab-vedotin-ejfv (EV).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06104618

Study Details | NCT06104618 | Enfortumab Vedotin for the ... This phase II trial tests how well enfortumab vedotin works for treating patients with squamous cell carcinoma of the penis that has spread to other places ...

3. 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% ...

4. 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.

5. apponcologysummit.org apponcologysummit.org/enfortumab-vedotin-ejfv-padcev/

Enfortumab vedotin-ejfv (PADCEV) Following a median duration of 10.2 months (range 0.5-16.5 months), results of the primary endpoint analysis showed an ORR of 44%, with 12% of patients ...

6. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-bladder-cancer/164052-esmo-2025-ev-103-cohort-k-efficacy-and-safety-of-enfortumab-vedotin-with-or-without-pembrolizumab-in-cisplatin-ineligible-patients-with-previously-untreated-locally-advanced-or-metastatic-urothelial-cancer-with-a-median-follow-up-of-3-5-years.html

ESMO 2025: EV-103 Cohort K: Efficacy and Safety ... 1st line EV+P continues to demonstrate durable responses, survival benefits, and a manageable safety profile in cisplatin-ineligible patients ...