Enfortumab Vedotin for the Treatment of Patients With Metastatic or Unresectable Squamous Cell Carcinoma of the Penis

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

What this study is about