ENFORTUMAB VEDOTIN for Penile squamous cell carcinoma (locally advanced or metastatic)

Inclusion criteria

• {"criterion_text":"- 1. Patient has ability to understand and the willingness to sign a written informed consent."}
• {"criterion_text":"- 10. 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."}
• {"criterion_text":"- 11. No history of significant cardiovascular disease (e.g., myocardial infarction, unstable angina) within the last 6 months."}
• {"criterion_text":"- 12. Life expectancy of at least 3 months."}
• {"criterion_text":"- 13. Willingness to comply with study requirements, including follow-up visits and procedures."}
• {"criterion_text":"- 14. 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."}
• {"criterion_text":"- 2. Patient is ≥ 18 years of age at time of signing the written informed consent."}
• {"criterion_text":"- 3. Male patients with histologically confirmed diagnosis of penile squamous cell carcinoma."}
• {"criterion_text":"- 4. 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: a.\tStage 3 (cT3) disease with a single lymph node involved (N1); b.\tStage 4 disease (cT4); c.\tAny 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."}
• {"criterion_text":"- 5. Tumor material (archival or current) is available for local pathology testing (PD-L1, HPV)."}
• {"criterion_text":"- 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2."}
• {"criterion_text":"- 7. Measurable disease per RECIST 1.1 criteria."}
• {"criterion_text":"- 8. 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."}
• {"criterion_text":"- 9. Patients has adequate blood count, liver-enzymes, and renal function: a.\tANC (Absolute neutrophil count) > 1,500 cells/μL without the use of hematopoietic growth factors; b.\tPlatelet count ≥ 100 x 109/L (>100,000 per mm3); c.\tHemoglobin ≥ 9 g/dL; d.\tSerum total bilirubin ≤ 1.5x institutional upper normal limit (ULN); e.\tAST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN (or ≤ 5 x ULN if liver metastases are present); f.\tCreatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault equation (or local institutional standard method)."}

Exclusion criteria

• {"criterion_text":"- 1. Previous systemic therapy for metastatic or locally advanced PeCa in the palliative setting."}
• {"criterion_text":"- 10. Severe hepatic impairment (Child-Pugh Class C)."}
• {"criterion_text":"- 11. Severe renal impairment or requirement for dialysis."}
• {"criterion_text":"- 12. History of keratitis and corneal ulceration in the last two years."}
• {"criterion_text":"- 13. Active pneumonia, pneumonitis or pulmonary fibrosis."}
• {"criterion_text":"- 14. Active tuberculosis."}
• {"criterion_text":"- 15. Known prior severe hypersensitivity to the study drugs or any component of their formulations, known severe hypersensitivity reactions to monoclonal antibodies (NCT CTCAE Grade ≥ 3)."}
• {"criterion_text":"- 16. Inability or unwillingness to comply with study requirements, including follow-up visits and procedures."}
• {"criterion_text":"- 17. Inability to provide informed consent."}
• {"criterion_text":"- 18. Use of immunosuppressive medication within 14 days prior to the first dose of study treatment, with the exception of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection), systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."}
• {"criterion_text":"- 19. Prior organ transplantation including allogenic stem-cell transplantation."}
• {"criterion_text":"- 2. Previous treatment with investigational drugs or devices within 30 days prior to the first dose of trial treatment."}
• {"criterion_text":"- 20. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines."}
• {"criterion_text":"- 21. Persisting toxicity related to prior therapy (NCI CTCAE Grade > 1); however, alopecia or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable."}
• {"criterion_text":"- 22. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study."}
• {"criterion_text":"- 23. Patient participated in another interventional clinical study according to Medicines Act within 28 days prior to study enrollment or participation in a clinical study according to Medicines Act at the same time as this study unless it is an observational / non-interventional study or during the follow-up period of an interventional study."}
• {"criterion_text":"- 3. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis."}
• {"criterion_text":"- 4. Active, known, or suspected autoimmune disease requiring systemic treatment within the past 2 years. Patients with controlled autoimmune disease not requiring systemic immunosuppressive treatment including diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases are eligible."}
• {"criterion_text":"- 5. Has ongoing sensory or motor neuropathy Grade 2 or higher."}
• {"criterion_text":"- 6. Has a history of uncontrolled diabetes (HbA1c > 8%)."}
• {"criterion_text":"- 7. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."}
• {"criterion_text":"- 8. Active infection requiring systemic therapy. The following exceptions apply: a. Patients with an HIV infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction. b. Patients with evidence of chronic HBV infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have ALT, AST, and total bilirubin levels < ULN, and provided there is no expected drug-drug interaction. c. Patients with a history of HCV infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels < ULN."}
• {"criterion_text":"- 9. History of other malignancies within the past 3 years, with the exception of adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin."}

Primary endpoints

• {"endpoint_text":"- Objective Response Rate (ORR) in 1st line as assessed by investigators, defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.","definition_or_measurement_approach":"Defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to RECIST 1.1 criteria, assessed by investigators."}

Secondary endpoints

• {"endpoint_text":"- Progression-free survival (PFS), defined as the time from the start of treatment to the first documented disease progression acc. to RECIST 1.1 criteria or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from start of treatment to first documented disease progression per RECIST 1.1 or death from any cause."}
• {"endpoint_text":"- Overall Survival (OS), defined as the time from the start of treatment to death from any cause.","definition_or_measurement_approach":"Time from start of treatment to death from any cause."}
• {"endpoint_text":"- Duration of Response (DoR), defined as the time from the first documented response (CR or PR) to disease progression or death from any cause, whichever occurs first.","definition_or_measurement_approach":"Time from first documented response (CR or PR) to disease progression or death."}
• {"endpoint_text":"- Disease Control Rate (DCR), defined as the proportion of patients achieving CR, PR, or stable disease (SD) according to RECIST 1.1 criteria.","definition_or_measurement_approach":"Proportion of patients achieving CR, PR, or stable disease per RECIST 1.1."}
• {"endpoint_text":"- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.","definition_or_measurement_approach":"Incidence and severity graded per CTCAE v5.0."}
• {"endpoint_text":"- Changes in patient-reported quality of life, using EQ-5D-5L and EQ-HWB-S questionnaire and a set of bolt-on questions will be collected.","definition_or_measurement_approach":"Patient-reported QoL measured using EQ-5D-5L and EQ-HWB-S questionnaires and additional bolt-on questions."}

Germany

Earliest CTIS Part Ii Submission Date

02-10-2025

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

174

Number Of Sites

10

Number Of Participants

25

Primary sponsor

Full Name

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Medicoline Pharma Solutions KG","duties_or_roles":"sponsor duties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Universitaetsklinikum Tuebingen AöR","duties_or_roles":"Translational Research; sponsor duties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}