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