Study of BMS-754807 Combined With Letrozole or BMS-754807 Alone in Patients With Hormone Receptor-Positive Breast Cancer and Resistance to Non-Steroidal Aromatase Inhibitors

Progression free survival (PFS) rate at 24 weeks after treatment with BMS 754807/letrozole was to be calculated as the total number of subjects neither progressed nor died after 24 weeks of treatment divided by the total number of subjects (with measurable or non-measurable disease) randomized/assigned to combination treatment arm and treated. In participants with measurable disease Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) criteria was to be used to assess disease progression.This outcome was not measured due to early termination of the study.

ORR is defined as the number of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) divided by the number of participants who received treatment. Participants were to be evaluated for tumor response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions.: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. This outcome measure was not met due to early termination of the study

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment.

DOR was to be performed to further characterize the response rate at Week 24. Duration of response is defined as the time between the Week 25 date of response and the date of objectively documented disease progression as defined by modified RECIST 1.1 criteria or death, whichever occurs first. DOR could not be assessed due to early termination of the study.

Blood and urine samples were obtained at specified times points for laboratory evaluations. Clinical Laboratory Sage Panels included: Hematology: Hemoglobin, Hematocrit, Red blood cell, Total leukocyte count, including differential, Platelet count. Serum Chemistry : Albumin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALK-P), Bilirubin, total (TB). Reflex testing of direct (conjugated) and indirect (unconjugated) bilirubin will be ordered if total bilirubin > 5X ULN, Blood urea nitrogen (BUN or urea), Calcium, Chloride, Cholesterol, Creatinine, serum, Glucose, fasting plasma, Lactate dehydrogenase (LDH), Magnesium, Phosphorus, Potassium, Protein, total, Sodium, Triglycerides, Uric acid Urinalysis, Blood, Glucose, Ketones, Leukocyte esterase, pH, Protein. Laboratory tests were graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0 criteria

Blood and urine samples were obtained at specified times points for laboratory evaluations. Clinical Laboratory Sage Panels included: Hematology: Hemoglobin, Hematocrit, Red blood cell, Total leukocyte count, including differential, Platelet count. Serum Chemistry : Albumin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALK-P), Bilirubin, total (TB). Reflex testing of direct (conjugated) and indirect (unconjugated) bilirubin will be ordered if total bilirubin > 5X ULN, Blood urea nitrogen (BUN or urea), Calcium, Chloride, Cholesterol, Creatinine, serum, Glucose, fasting plasma, Lactate dehydrogenase (LDH), Magnesium, Phosphorus, Potassium, Protein, total, Sodium, Triglycerides, Uric acid Urinalysis, Blood, Glucose, Ketones, Leukocyte esterase, pH, Protein Laboratory tests were graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE), Version 4.0 criteria

The TFR was to be calculated as the total number of subjects who discontinued the treatment for any reason (including disease progression, treatment toxicity, and death) at 24 weeks divided by the total number of subjects randomized/assigned to the arm and treated. In the monotherapy arm, the TFR was to be assessed while subjects were on monotherapy.

Absolute copy numbers and relative expression of insulin receptor isoforms (IR-A, IR-B) in pre- and posttreatment fresh tumor tissues were to be measured. This outcome was not measured due to early termination of the study.