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

Trial Summary

What is the purpose of this trial?

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 in the body (metastatic) or cannot be removed by surgery (unresectable). Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them.

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.

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

A case study showed that Enfortumab Vedotin, which targets a protein called Nectin-4 found in many squamous cell carcinomas, helped a patient with advanced penile cancer improve after other treatments failed. This suggests it might be a promising option for this rare and difficult-to-treat cancer. ^{1 2 3 4 5}

Is Enfortumab Vedotin safe for humans?

There is limited safety data specifically for Enfortumab Vedotin in penile cancer, but it has been used in other cancers with some success. In one case, a patient with penile cancer showed improvement after treatment with Enfortumab Vedotin, suggesting it may be safe, but more studies are needed to confirm this. ^{1 2 3 6 7}

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

Enfortumab Vedotin is unique because it targets Nectin-4, a protein highly expressed in penile squamous cell carcinoma, and is an antibody-drug conjugate (ADC) that combines an antibody with a cancer-killing drug. This approach is different from traditional chemotherapy and offers a new option for patients with advanced penile cancer who have limited treatment choices. ^{1 2 3 8 9}

Research Team

Lance C. Pagliaro

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Metastatic Penile Squamous Cell Carcinoma Responsive to Enfortumab Vedotin. [2023]

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

Panitumumab Treatment for Advanced Penile Squamous Cell Carcinoma When Surgery and Chemotherapy Have Failed. [2022]

3. England pubmed.ncbi.nlm.nih.gov

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Systemic treatment of locally advanced or metastatic penile cancer]. [2020]

5. United States 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. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience. [2023]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A case of penile squamous cell carcinoma treated with a combination of antiepidermal growth factor receptor antibody and chemotherapy. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Epidermal growth factor receptor-targeted therapy in locally advanced or metastatic squamous cell carcinoma of the penis. [2022]