Study to Evaluate the Safety and Tolerability of IV Doses of BMS-906024 in Subjects With Advanced or Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to identify a safe and tolerable dose of BMS-906024 in subjects with advanced or metastatic solid tumors who no longer respond to or have relapsed from standard therapies.

Official Title
-----------------
Phase 1 Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-906024 in Subjects With Advanced Solid Tumors

Conditions
-----------------
Cancer

Intervention / Treatment
-----------------
* Drug: BMS-906024


Participation Criteria
=================
Eligibility Criteria
-----------------
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: Subjects with advanced or metastatic solid tumors (non-hematologic refractory to or relapsed from standard therapies or for which there is no known effective treatment during dose escalation Subjects with squamous non-small cell lung cancer and triple-negative breast cancer or other solid tumor types for which Notch activation has been demonstrated (such as pancreatic, ovarian and melanoma) during dose expansion Biopsy accessible tumor (may be waived under certain circumstances) Life expectancy of at least 3 months Eastern Cooperative Oncology Group (ECOG) 0-1 Adequate organ and bone marrow function Exclusion Criteria: Infection Elevated triglycerides Gastrointestinal (GI) disease with increased risk of diarrhea [e.g. inflammatory bowel disease (IBD)] Taking medications known to increase risk of Torsades De Pointes

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A1 (Escalation): BMS-906024<br>BMS-906024 solution intravenously as specified | Drug: BMS-906024<br> <br> * Other names: BMS-906024 (Notch inhibitor);|
| Experimental: Arm A2 (Expansion): BMS-906024<br>BMS-906024 solution intravenously as specified | Drug: BMS-906024<br> <br> * Other names: BMS-906024 (Notch inhibitor);|
| Experimental: Arm B1 (Escalation): BMS-906024<br>BMS-906024 solution intravenously as specified | Drug: BMS-906024<br> <br> * Other names: BMS-906024 (Notch inhibitor);|
| Experimental: Arm B2 (Expansion): BMS-906024<br>BMS-906024 solution intravenously as specified | Drug: BMS-906024<br> <br> * Other names: BMS-906024 (Notch inhibitor);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability |  | Weekly assessments until study discontinuation due to disease progression or unacceptable adverse event as well as an assessment 30 day after treatment discontinuation with an average time on study expected to be <1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor assessments using response evaluation criteria in solid tumors (RECIST) v1.1 |  | Tumor assessments at least every 8 weeks during treatment period | 
| PD changes from baseline in the expression of Notch pathway-related genes in surrogate tissues (peripheral blood cells) and tumor biopsies |  | PD changes from baseline during the first 4-5 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, maximum observed concentration (Cmax) |  | PK at multiple time points during the first 8 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, minimum observed concentration (Cmin) |  | PK at multiple time points during the first 8 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, time to reach maximum observed concentration (Tmax) |  | PK at multiple time points during the first 8 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, terminal phase elimination half-life (T-Half) |  | PK at multiple time points during the first 8 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, accumulation index (AI) |  | PK at multiple time points during the first 8 weeks of dosing | 
| PK parameters for BMS-906024 and its metabolite BMS-911557, area under the concentration-time curve (AUC) |  | PK at multiple time points during the first 8 weeks of dosing |