Phase I/Ib Multiple Ascending Dose Study in China

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of Avelumab monotherapy in Chinese subjects.

Official Title
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A Phase I/Ib Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Avelumab in Chinese Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors With Expansion to Selected Indication(s)

Conditions
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Metastatic Solid Tumors

Intervention / Treatment
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* Drug: Avelumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent prior to any study-related procedures are undertaken that are not part of standard patient management Histologically or cytologically proven locally advanced unresectable or metastatic solid tumors, for which no standard therapy exists or standard therapy has failed Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry Availability of a recently obtained formalin-fixed, paraffin-embedded block containing tumor tissue (biopsy from a non-irradiated area within 6 months) or 12 or more unstained tumor slides suitable for biomarker detection Other protocol defined inclusion criteria could apply Exclusion Criteria: Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as programmed death 1 (PD-1), PD-L1, cytotoxic T-lymphocyte antigen-4 (CTLA-4), 4-1BB, Lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) or anti-Cluster of Differentiation (CD)-127 Persisting toxicity related to prior therapy (Grade greater than equals to [>=] 2 National Cancer Institute- Common Terminology Criteria for Adverse Events [NCI-CTCAE] v4.03, except Grade less than [<] 3 neuropathy and alopecia of any grade) Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of limited palliative bone-directed radiotherapy], immune therapy, or cytokine therapy except for erthyropoietin). Concurrent immunosuppressive agents (except for corticosteroids at physiologic replacement dose, equivalent to less than equals to [<=] 10 milligram [mg] prednisone daily) Severe hypersensitivity reactions to monoclonal antibodies (Grade >= 3 NCI-CTCAE v4.03) Active brain metastases (except those treated locally, and have not been progressing for at least 2 weeks after the completion of therapy, with no steroid maintenance therapy required, and no ongoing neurological symptoms related to brain localization of the disease) Any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Sequential Assignment
Interventional Model Description: Subsequent cohorts of subjects treated at different dose levels in this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avelumab<br> | Drug: Avelumab<br>* Subjects will receive an intravenous infusion of avelumab once every 2 weeks (q2w) or every week for the first 12 weeks and then q2w from Week 13 until progressive disease.<br>* Other names: MSB0010718C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Dose-limiting Toxicities (DLTs) |  | Time from first treatment to planned assessment at Day 21 | 
| Area Under the Concentration-Time Curve From Time Zero to Time t (AUC0-t) of Avelumab |  | Up to Month 15 | 
| Area Under the Concentration-Time Curve From Time Zero to tau (AUC0-tau) of Avelumab |  | Up to Month 15 | 
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Avelumab |  | Up to Month 15 | 
| Terminal Elimination Rate Constant (λz) of Avelumab |  | Up to Month 15 | 
| Maximum Observed Serum Concentration (Cmax) of Avelumab |  | Up to Month 15 | 
| Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab |  | Up to Month 15 | 
| Last Quantifiable Concentration (Clast) of Avelumab |  | Up to Month 15 | 
| Time to Reach Maximum Observed Serum Concentration (Tmax) for Avelumab |  | Up to Month 15 | 
| Serum Decay Half-Life (t1/2) of Avelumab |  | Up to Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Treatment-Emergent Adverse Events (AEs) and Treatment Related AEs According to National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03 |  | Time from first dose of study drug up to Day 175 | 
| Anti-Drug Antibodies (ADAs) Serum Titers |  | Up to Day 115 | 
| Number of Subjects With Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) |  | Up to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Solid Tumors, Avelumab, MSB0010718C