DEPECA-1 - DEfeating PEnile Cancer 1 - A Phase II Study to Evaluate a First-line Systemic Therapy With Enfortumab Vedotin Plus Avelumab for Advanced and Metastatic Penile Carcinoma
The DEPECA-1 trial is the first systematic Phase II trial to evaluate response and survival to a combination of antibody-drug conjugate enfortumab vedotin plus the PD-L1 inhibitor avelumab in patients with locally advanced and metastatic penile squamous cell carcinoma (PeCa) in the 1st line setting.
• Patient has ability to understand and the willingness to sign a written informed consent.
• Patient is ≥ 18 years of age at time of signing the written informed consent.
• Male patients with histologically confirmed diagnosis of penile squamous cell carcinoma.
• Patients must be considered non-eligible for curative surgical management. Eligibility for trial inclusion should be based on the presence of either distant metastatic disease (M1) or at least one of the following scenarios based on the UICC/AJCC 8th edition TNM clinical and pathological classification of penile cancer:
∙ Stage 3 (cT3) disease with a single lymph node involved (N1).
‣ Stage 4 disease (cT4).
‣ Any T stage with either N2 (involvement of multiple or bilateral inguinal nodes) or N3 (fixed inguinal nodal mass or pelvic lymphadenopathy) disease. Patients without distant metastases are eligible if multidisciplinary team review concludes that they are unsuitable for curative surgery.
• Tumor material (archival or current) is available for local pathology testing (PD-L1, HPV).
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Measurable disease per RECIST 1.1 criteria.
• No prior systemic therapy for metastatic or locally advanced PeCa in the palliative setting. NOTE: (Neo)adjuvant systemic therapy (without IO) is allowed at least 6 months before study enrollment.
• Patients has adequate blood count, liver-enzymes, and renal function:
∙ ANC (Absolute neutrophil count) \> 1,500 cells/μL without the use of hematopoietic growth factors.
‣ Platelet count ≥ 100 x 109/L (\>100,000 per mm3).
‣ Hemoglobin ≥ 9 g/dL.
‣ Serum total bilirubin ≤ 1.5x institutional upper normal limit (ULN).
‣ AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN (or ≤ 5 x ULN if liver metastases are present).
‣ Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft- Gault equation (or local institutional standard method).
⁃ No other active malignancy within the past 3 years, except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin.
⁃ No history of significant cardiovascular disease (e.g., myocardial infarction, unstable angina) within the last 6 months.
⁃ Life expectancy of at least 3 months.
⁃ Willingness to comply with study requirements, including follow-up visits and procedures.
⁃ Patients with female partners of childbearing potential must agree to use an effective method of contraception during the study and for 4 months after the last dose of enfortumab vedotin or for at least 30 days after last avelumab treatment administration, whichever occurs last.