A Phase 1/2 Randomized, Blinded, Placebo Controlled Study of Ipilimumab in Combination With Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma

Study Overview
=================
Brief Summary
-----------------
The study design includes an open-label, dose escalation phase followed by a blinded, randomized phase, which combines epacadostat (an oral IDO1 inhibitor) with an approved therapy and compares to approved therapy plus placebo in metastatic melanoma patients.

Official Title
-----------------
A Phase 1/2 Randomized, Blinded, Placebo Controlled Study of Ipilimumab in Combination With Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma

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

Intervention / Treatment
-----------------
* Drug: Epacadostat
* Drug: Placebo
* Drug: ipilimumab
* Drug: ipilimumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects, aged 18 years or older with unresectable or metastatic melanoma. A life expectancy of >12 weeks. Laboratory ranges and medical criteria met, as defined within the protocol. Subject may have received more than 1 prior regimen of systematic treatment for unresectable or metastatic melanoma. For Phase 2 period of the study only, Subjects must have archival tumor tissue available and collected with the prior 6 months or accessible disease for pre-treatment, study biopsy. Exclusion Criteria: Pregnant or nursing women. Current investigational trial participation with another investigational product or subjects who have received any anticancer medications within 21 days prior to screening (6 weeks for mitomycin-C or nitrosoureas.) Subjects receiving monoamine oxidase inhibitors (MAOI)s; subjects who have ever had Serotonin Syndrome after receiving one or more serotonergic drugs. Subjects who have received prior immune checkpoint inhibitors (eg anti-CTLA-4, anti-PD-1, anti- PD-L1 and others) who have had Grade 3 or 4 hepatotoxicity, immune colitis requiring infliximab, endocrine toxicity not controlled by replacement, any other Grade 4 immune adverse events (AEs) or ocular toxicity Subjects with protocol-specified active autoimmune process except vitiligo or thyroiditis. Subjects with concurrent conditions that would jeopardize the safety of the safety of the subject or compliance with the protocol.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epacadostat 300 mg<br>300 mg twice daily (BID) in combination with ipilimumab | Drug: Epacadostat<br> <br> * Other names: INCB024360;Drug: ipilimumab<br>* Doses to be determined following the completion of Phase I of the study<br>|
| Placebo Comparator: Placebo in combination with ipilimumab<br> | Drug: Placebo<br>* Placebo<br>Drug: ipilimumab<br>* ipilimumab 3 mg/kg IV<br>|
| Experimental: Epacadostat 25 mg<br>25 mg BID in combination with ipilimumab | Drug: Epacadostat<br> <br> * Other names: INCB024360;Drug: ipilimumab<br>* Doses to be determined following the completion of Phase I of the study<br>|
| Experimental: Epacadostat 50 mg<br>50 mg BID in combination with ipilimumab | Drug: Epacadostat<br> <br> * Other names: INCB024360;Drug: ipilimumab<br>* Doses to be determined following the completion of Phase I of the study<br>|
| Experimental: Epacadostat 75 mg<br>75 mg once a day (QD) in combination with ipilimumab | Drug: Epacadostat<br> <br> * Other names: INCB024360;Drug: ipilimumab<br>* Doses to be determined following the completion of Phase I of the study<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of patients with adverse events as a measure of Safety and Tolerability. |  | Baseline and minimally every 3 weeks until discontinuation or death (estimated timeframe to be 29 months from first patient enrolled to last patient discontinued or dead). | 
| Phase 2: Overall survival. |  | Measured every 4 weeks until the 50th death occurs, then follow-up is measured every 3 months (estimated timeframe to be 29 months from first patient enrolled to last patient death). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary efficacy as assessed by tumor response. |  | Baseline and every nine weeks (3 cycles) thereafter (estimated timeframe is that each patient will be on study for 11 months). | 
| Evaluation of progression free survival. |  | Measured every 4 weeks until the 50th death occurs, then follow-up is measured every 3 months (estimated timeframe is that patients will progress after 11 months). | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Melanoma, Skin Cancer, Oncology