A Study of Avelumab in Penile Cancer Who Are Unfit for or Have Progressed After Platinum-Based Chemotherapy

Study Overview
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Brief Summary
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This is a phase 2 study whose purpose is see how useful investigational drug, avelumab, is in patients with locally advanced or metastatic penile cancer who are unfit for or progressed on platinum-based chemotherapy. The usefulness of avelumab in this study population will be determined by anti-tumor activity assessed by objective response rate. Avelumab is a monoclonal antibody that binds to a protein called programmed death-ligand 1 (PD-L1) and blocks its communication with another protein called programmed death protein 1 (PD-1). The communication of these proteins are thought to be important in the growth of tumors. Blocking these proteins from communicating may stop or shrink tumors.

Official Title
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A Phase 2, Multi-centre, Open-label Study of Avelumab (MSB0010718C) in Locally Advanced or Metastatic Penile Cancer Patients Unfit for Platinum-based Chemotherapy or Progressed On or After Platinum-based Chemotherapy

Conditions
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Penile Cancer, Advanced Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: Avelumab
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed squamous cell carcinoma of the penis Measurable disease per Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) Unresectable/metastatic disease that is unfit for platinum-based chemotherapy OR disease that has progressed on or after treatment with platinum-based chemotherapy ≥18 years of age Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Exclusion Criteria: Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways Major surgery ≤4 weeks or major radiation therapy ≤2 weeks prior to enrollment Known symptomatic central nervous system (CNS) metastases requiring steroids Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avelumab and Best Supportive Care<br>Avelumab will be given intravenously (by vein) at a dose of 10 mg/kg, once every 2 weeks Best supportive care will be provided as required. | Drug: Avelumab<br>* Avelumab is a fully human monoclonal antibody (mAb) of the immunoglobulin (Ig) G1 isotype. Avelumab selectively binds to programmed death-ligand 1 (PD-L1) and competitively blocks its interaction with programmed death protein 1 (PD-1).<br>Other: Best Supportive Care<br>* As required.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | To demonstrate the anti-tumor activity of avelumab by objective response rate (ORR) according to Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST) in patients with locally advanced or metastatic penile carcinoma unfit for platinum-based chemotherapy or progressed on or after platinum-based chemotherapy. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Rate | Assess the progression free survival (PFS) of avelumab in patients determined to have PD-L1-positive tumors (including infiltrating immune cells) by the GMP verified Dako PD-L1 IHC 22C3 pharmDx test with thresholds of <1%, 1-49%, and ≥ 50% to define PD-L1 positivity, and in all enrolled patients | 3 years | 
| Overall Survival Rate | Assess the overall survival (OS) of avelumab in patients determined to have PD-L1-positive tumors (including infiltrating immune cells) by the GMP verified Dako PD-L1 IHC 22C3 pharmDx test with thresholds of <1%, 1-49%, and ≥ 50% to define PD-L1 positivity, and in all enrolled patients | 3 years |