Combination of Anti-CD137 & Ipilimumab in Patients With Melanoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if BMS-663513 administered in combination with ipilimumab to patients with advanced malignant melanoma is safe and tolerable

Official Title
-----------------
A Phase I, Multiple Ascending Dose Study of BMS-663513 (Anti CD137) in Combination With Ipilimumab (BMS-734016/Anti-CTLA-4) in Subjects With Unresectable Stage III or Stage IV Melanoma

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Drug: AntiCD137
* Drug: AntiCD137
* Drug: AntiCD137
* Drug: AntiCD137
* Drug: AntiCD137
* Drug: Ipilimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed malignant melanoma Stage III (unresectable) or Stage IV disease which may have been treated with up to one prior cytotoxic chemotherapy and/or up to 3 other therapeutic regimens Willing to undergo up to 3 biopsies of an accessible lesion Exclusion Criteria: Active/symptomatic brain metastases Primary ocular melanoma or primary tumor of unknown origin Concurrent autoimmune disease Previous treatment with a CD137 agonist or CTLA-4 inhibitor

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: 0.1 mg/kg<br> | Drug: AntiCD137<br>* Infusion, IV, 0.1 mg/kg, Q3 weeks for 12 weeks then Q12 weeks, 12+ weeks depending on response<br>* Other names: BMS-663513;Drug: Ipilimumab<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12, 12+ weeks depending on response<br>* Other names: MDX-010;|
| Experimental: 0.3 mg/kg<br> | Drug: AntiCD137<br>* Infusion, IV, 0.3 mg/kg, Q3 weeks for 12 weeks then Q12 weeks, 12+ weeks depending on response<br>* Other names: BMS-663513;Drug: Ipilimumab<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12, 12+ weeks depending on response<br>* Other names: MDX-010;|
| Experimental: 1.0 mg/kg<br> | Drug: AntiCD137<br>* Infusion, IV, 1.0 mg/kg, Q3 weeks for 12 weeks then Q12 weeks, 12+ weeks depending on response<br>* Other names: BMS-663513;Drug: Ipilimumab<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12, 12+ weeks depending on response<br>* Other names: MDX-010;|
| Experimental: 3.0 mg/kg<br> | Drug: AntiCD137<br>* Infusion, IV, 3.0 mg/kg, Q3 weeks for 12 weeks then Q12 weeks, 12+ weeks depending on response<br>* Other names: BMS-663513;Drug: Ipilimumab<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12, 12+ weeks depending on response<br>* Other names: MDX-010;|
| Experimental: 10 mg/kg<br> | Drug: AntiCD137<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12 weeks, 12+ weeks depending on response<br>* Other names: BMS-663513;Drug: Ipilimumab<br>* Infusion, IV, 10 mg/kg, Q3 weeks for 12 weeks then Q12, 12+ weeks depending on response<br>* Other names: MDX-010;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of safety and tolerability as determined by analysis of adverse event reports and results of vital sign measurements, physical examinations, and clinical laboratory tests |  | During the course of the each subject's treatment and up to 70 days after his or her last dose of study medication is received | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of clinical improvement in tumor burden confirmed by CT or MRI |  | Weeks 12, 18, 24, 30, 36, 42, 48, and every 12 weeks thereafter |