Treatment for advanced penile squamous cell carcinoma using enfortumab vedotin

Phase II Study of Enfortumab Vedotin Treatment for Metastatic Squamous Cell Carcinoma of the Penis

This study tests if a new treatment called enfortumab vedotin can help people with advanced penile cancer live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: enfortumab, chemotherapy, immunotherapy, prednisone
• Locations: 3 sites (Phoenix, Arizona and 2 other locations)
• Trial ID: NCT06104618 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of enfortumab vedotin in treating patients with metastatic or unresectable squamous cell carcinoma of the penis. The treatment involves administering enfortumab vedotin intravenously, which targets tumor cells by attaching to a specific protein and delivering an anticancer drug. The study aims to assess the best response rate, overall response rate, safety, and duration of response, as well as overall and progression-free survival rates. Patients will undergo imaging studies throughout the trial to monitor their condition.

Who should consider this trial

Good fit: Ideal candidates include adult men aged 18 and older with confirmed metastatic or unresectable squamous cell carcinoma of the penis.

Not a fit: Patients with localized penile cancer that can be surgically removed or those without histological confirmation of squamous cell carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced penile cancer, potentially improving survival rates.

How similar studies have performed: Other studies have shown promise with targeted therapies in similar cancer types, suggesting potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Histological confirmation of squamous cell carcinoma of the penis (PSCC): NOTE: Biopsy confirmation of at least one site of metastasis is encouraged but not required.
* At least one site of metastatic or unresectable PSCC. NOTE: Prior therapy is not required for patients whose treatment is considered palliative (for example, presence of distant metastasis). NOTE: Patients who are potentially curable (any T, N1 - N3, M0) must have had tumor progression after standard chemotherapy, radiotherapy, or surgery, or be unable to receive such treatment. Eligible stages include:

  * Any T, N1 (i.e., a palpable mobile unilateral inguinal lymph node), M0 OR
  * Any T, N2 (i.e., palpable mobile multiple or bilateral inguinal lymph nodes), M0 OR
  * Any T, N3 (i.e., fixed inguinal nodal mass or any pelvic lymphadenopathy), M0 OR
  * Any T, any N, M1
* Patients with clinical N1, M0 mPSCC at protocol entry must be ineligible for surgery because of comorbidities or clinical T4 disease, or have refused surgery
* Patients with clinical N1 - N3, M0, and no prior systemic therapy must be:

  * Unable to receive neoadjuvant (paclitaxel + ifosfamide + cisplatin) TIP because of comorbidities or refused TIP; AND
  * Unable to receive radiotherapy with curative intent, or refused radiotherapy
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
* Prior therapy is allowed. Patients may be treatment-naïve or have had any number of prior anti-cancer treatments
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
* Hemoglobin ≥ 9.0 g/dL obtained ≤15 days prior to registration
* Absolute neutrophil count (ANC) ≥ 1000/mm\^3 obtained ≤ 15 days prior to registration
* Platelet count ≥ 100,000/mm\^3 obtained ≤ 15 days prior to registration
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for patients with Gilbert's disease obtained ≤ 15 days prior to registration
* Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN obtained ≤ 15 days prior to registration
* Glomerular filtration rate (GFR) or calculated creatinine clearance ≥ 30 ml/min as estimated using the Cockcroft-Gault formula or as measured by 24-hour urine collection obtained ≤ 15 days prior to registration
* Provide written informed consent
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria:

* Pure verrucous carcinoma of the penis
* Non-squamous malignancy of the penis
* Squamous carcinoma of the urethra
* Preexisting sensory or motor neuropathy ≥ grade 2
* Active central nervous system (CNS) metastases. Exception: Treated CNS metastases are allowed if all of the following are true:

  * CNS metastases are clinically stable for ≥ 6 weeks prior to registration
  * If needed, steroid dose is stable and ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks prior to registration
  * Baseline imaging shows no evidence of new or enlarged brain metastasis
  * No leptomeningeal disease
* History of uncontrolled diabetes mellitus ≤ 3 months prior to registration NOTE: Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8.0% or HbA1c 7.0-7.9% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
* Failure to recover from any of the following therapies prior to registration:

  * Major surgery
  * Radiotherapy, chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
* Uncontrolled intercurrent illness including, but not limited to:

  * Ongoing or active infection requiring systemic treatment
  * History of cerebral vascular event (stroke or transient ischemic attack)
  * Myocardial infarction or symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III-IV) ≤ 6 months prior to registration
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Or psychiatric illness/social situations that would limit compliance with study requirements (e.g., history of substance abuse)
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection. NOTE: Routine antimicrobial prophylaxis is allowed
* Known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or active hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid (RNA) \[qualitative\] is detected)
* Known active keratitis or corneal ulcerations. NOTE: Superficial punctate keratitis is allowed if the disorder is being adequately treated
* Known hypersensitivity to enfortumab vedotin or to any excipient contained in the drug formulation of enfortumab vedotin (including histidine, trehalose dihydrate and polysorbate 20) OR subject has known hypersensitivity to biopharmaceutical produced in Chinese hamster ovary cells
* Other active malignancy ≤ 2 years prior to registration. EXCEPTIONS: Locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, or carcinoma in situ of the breast or low risk Gleason 6 prostate cancer.
* History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* Patients who are sexually active and unwilling to use effective contraception (if they are not already surgically sterile)
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Chemotherapy-naïve patients who are potentially curable (any T, N1 - N3, M0) in the absence of any condition that precludes cisplatin-based chemotherapy, such as low GFR, peripheral neuropathy, hearing impairment, or psychosocial considerations

Where this trial is running

Phoenix, Arizona and 2 other locations

• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (Recruiting)
• Mayo Clinic in Florida — Jacksonville, Florida, United States (Recruiting)
• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Lance C. Pagliaro, M.D. — Mayo Clinic in Rochester
• Study coordinator: Clinical Trials Referral Office

Conditions Metastatic Penile Squamous Cell Carcinoma; Stage III Penile Cancer AJCC v8; Stage IV Penile Cancer AJCC v8; Unresectable Penile Squamous Cell Carcinoma