Multiple Ascending Dose (MDX1105-01)

Study Overview
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Brief Summary
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Collection of survival data, evaluation of PDL-1 expression in tumors, and evaluation of PD-L1 receptor occupancy in peripheral blood has been added.

Detailed Description
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This is an open label, multicenter, dose escalation and multidose study of MDX-11-5, a fully human monoclonal IgG4 antibody targeting the Programed Death-Ligand 1 (PD-L1). The study will consist of 3 periods: Screening (up to 28 days), Treatment (up to 16 six-week cycles), and Follow-up (up to 6 months).

Official Title
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A Phase 1, Multidose Study of BMS-936559 (MDX-1105) Administered Every 14 Days in Subjects With Selected Advanced or Recurrent Solid Tumors

Conditions
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Cancer, Multiple Indications

Intervention / Treatment
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* Biological: Anti-PDL-1 antibody
* Biological: Anti-PDL-1 antibody
* Biological: Anti-PDL-1 antibody
* Biological: Anti-PDL-1 antibody
* Biological: Anti-PDL-1 antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 The malignancies include relapsed/refractory renal cell carcinoma, non-small cell lung cancer, colorectal adenocarcinoma, malignant melanoma, advanced/metastatic epithelial ovarian cancer, gastric cancer, pancreatic cancer and breastcancer Must have measurable disease Exclusion Criteria: Prior therapy with an anti-PD 1, anti-PDL 1, or anti-Cytotoxic T-Lymphocyte Antigen 4 antibody (or any other agents that target T-cell co-stimulation)

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-PDL-1 antibody (Arm 1)<br>BMS-936559 (MDX-1105) | Biological: Anti-PDL-1 antibody<br>* Solution, Intravenous, 0.1 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response<br>* Other names: MDX 1105;|
| Experimental: Anti-PDL-1 antibody (Arm 2)<br>BMS-936559 (MDX-1105) | Biological: Anti-PDL-1 antibody<br>* Solution, Intravenous, 0.3 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response<br>* Other names: MDX 1105;|
| Experimental: Anti-PDL-1 antibody (Arm 3)<br>BMS-936559 (MDX-1105) | Biological: Anti-PDL-1 antibody<br>* Solution, Intravenous, 1 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response<br>* Other names: MDX 1105;|
| Experimental: Anti-PDL-1 antibody (Arm 4)<br>BMS-936559 (MDX-1105) | Biological: Anti-PDL-1 antibody<br>* Solution, Intravenous, 3 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response<br>* Other names: MDX 1105;|
| Experimental: Anti-PDL-1 antibody (Arm 5)<br>BMS-936559 (MDX-1105) | Biological: Anti-PDL-1 antibody<br>* Solution, Intravenous, 10 mg/kg, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles/48 doses depending on response<br>* Other names: MDX 1105;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, maximum tolerated dose (MTD) and dose-limiting toxicity(DLT)of MDX-1105 |  | Weekly | 
| Safety, maximum tolerated dose (MTD) and dose-limiting toxicity(DLT)of MDX-1105 |  | Bi-weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy in solid tumors on the basis of objective responses |  | Day 42 |