A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of BMS-833923 (XL139) in patients with advanced or metastatic cancers and determine the recommended phase 2 dose range and schedule

Official Title
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A Phase 1 Multiple Ascending Dose Study of BMS-833923 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Hedgehog Pathway, Smoothened, Basal Cell Carcinoma (BCC), Basal Cell Nevoid Syndrome (BCNS)

Intervention / Treatment
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* Drug: BMS-833923 (XL139)


Participation Criteria
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Eligibility Criteria
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For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Inclusion Criteria: Advanced or metastatic cancer (excluding cancer in the blood) or uncontrolled basal cell nevoid syndrome or sporadic basal cell carcinoma Primary or metastatic tumor site accessible for biopsy Ability to swallow capsules Subjects with histologically confirmed, advanced stage IIIB or stage IV non-small cell lung cancer (NSCLC) with a primary histology of squamous carcinoma who have received prior systemic therapy for advanced NSCLC will be enrolled in Part 3 Exclusion Criteria: Uncontrolled brain metastasis Significant cardiovascular disease Inadequate blood counts Inadequate liver, kidney or lung function Gastrointestinal disease within last 3 months Infection with Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C or exposure to attenuated active immunizations

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-833923<br> | Drug: BMS-833923 (XL139)<br>* Capsules, Oral, 30 mg starting; dose escalation, Once daily, 37 days; additional days if receiving benefit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) to establish the maximum tolerated dose, a recommended Phase 2 dose range and schedule, and safety profile of BMS-833923 | Use NCI CTCAE to monitor safety assessments including physical findings, laboratory tests, and radiographic assessments to establish the maximum tolerated dose and recommended Phase 2 dose range and schedule of BMS-833923 | On average a minimum of 60 days up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Maximum observed plasma concentration (Cmax) |  | Study day 1-7, 36 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose and during daily dosing: Time of maximum observed plasma concentration (Tmax) |  | Study day 1-7, 36 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)] of BMS-833923 (XL139) |  | Study day 1-7 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-833923 (XL139) |  | Study day 1-7 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) following a single-dose: Plasma half-life (T-HALF) of BMS-833923 (XL139) |  | Study day 1-7 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Minimum observed plasma concentration (Cmin) of BMS-833923 (XL139) |  | Study day 1, 8, 15, 22, 29, 36, 64, and 92 | 
| Pharmacokinetic parameters of BMS-833923 (XL139) during daily dosing: Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-833923 (XL139) |  | Study day 36 | 
| To assess the pharmacodynamic effects of BMS-833923 (XL139) on Hedgehog (HH) pathway activation in skin by evaluation of biomarkers such as, but not limited to GLI-1 protein or mRNA expression using immunohistochemistry (IHC) or RT-PCR in a skin biopsies | glioma-associated oncogene family of transcription factors (GLI) | At screening (baseline) and between days 22 and 36 of treatment | 
| To assess the pharmacodynamic effects of BMS-833923 (XL139) on HH pathway activation in subjects' tumors by evaluation of protein and mRNA of biomarkers such as, but not limited to GLI-1, in pre- and during-treatment tumor samples | glioma-associated oncogene family of transcription factors (GLI) | At screening (baseline) and between days 22 and 36 of treatment. At screening only for NSCLC patients | 
| To describe any preliminary evidence of anti-tumor activity of BMS-833923 (XL139) | Tumor assessments by computed tomography (CT) | Every 8 weeks until disease progression | 
| Safety profile of multiple doses of BMS-833923 | Medical review of adverse event reports | Adverse event reports: On average a minimum of 60 days up to 3 years | 
| Safety profile of multiple doses of BMS-833923 | The results of vital sign measurements, electrocardiogram (ECGs), pulmonary function tests, multigated radionuclide angiography (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests | Conducted at least on days 1, 8, 15, 22 and 36 of the first 36-day cycle and then monthly or biweekly for the first 6 months, then monthly |