Phase 1 Biomarker Study of Anti-PDL-1 in Advanced Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate pharmacodynamic changes of BMS-936559 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with unresectable Stage III or IV Melanoma.

Official Title
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A Phase I Study of the Biologic Effects of BMS-936559 Treatment in Subjects With Unresectable Stage III or IV Melanoma

Conditions
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Stage III or IV Melanoma

Intervention / Treatment
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* Biological: BMS-936559 (Anti-PD-L1)
* Biological: BMS-936559 (Anti-PD-L1)
* Biological: BMS-936559 (Anti-PD-L1)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years Eastern Cooperative Oncology Group (ECOG) status = 0 to 1 Subjects with unresectable Stage III or IV Melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic Melanoma Subject must have histologic or cytologic confirmation of advanced Melanoma Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies Exclusion Criteria: Active or progressing brain metastases Other concomitant malignancies (with some exceptions per protocol) Active or history of autoimmune disease Positive test for human immunodeficiency virus (HIV) 1&2 or known acquired immunodeficiency syndrome (AIDS) History of any hepatitis Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti Programmed cell death 1 (PD-1), anti Programmed cell death ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40 or anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibodies

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: BMS-936559 (1mg/kg)<br> | Biological: BMS-936559 (Anti-PD-L1)<br>* Solution, Intravenous infusion, 1 mg/kg, Every 2 weeks, Up to 2 years, depending on response<br>* Other names: MDX1105;|
| Experimental: Arm 2: BMS-936559 (3mg/kg)<br> | Biological: BMS-936559 (Anti-PD-L1)<br>* Solution, Intravenous infusion, 3 mg/kg, Every 2 weeks, Up to 2 years, depending on response<br>* Other names: MDX1105;|
| Experimental: Arm 3: BMS-936559 (10mg/kg)<br> | Biological: BMS-936559 (Anti-PD-L1)<br>* Solution, Intravenous infusion, 10 mg/kg, Every 2 weeks, Up to 2 years, depending on response<br>* Other names: MDX1105;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of immunomodulatory effects of BMS-936559 as measured by changes from baseline in biomarkers assessed 1) peripheral blood assays including flow cytometry and soluble factors and 2) tumor based assays including immunohistochemistry |  | Baseline and within the first 24 weeks of study participation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of BMS-936559 as measured by the incidence of adverse events (AEs), serious AEs, laboratory test abnormalities, and changes in vital signs |  | Every 2 weeks until 70 days after last treatment | 
| Antitumor Activity of BMS-936559 as measured by the objective response rate, disease control rate, duration of response, and progression free survival |  | Every 6 weeks for 1 year, every 12 weeks thereafter until confirmed disease progression | 
| Immunogenicity of BMS-936559 as measured by the frequency of subjects with an increase in anti-drug antibody levels from baseline |  | Baseline, Week 6, Week 12, and then every 12 weeks until follow-up | 
| Pharmacodynamic activity of BMS-936559 as measured by changes from baseline of the tetramer assay in HLA-A*0210 positive subject only |  | Predose (screening) and Cycle 3 Day 1 |