Curis Hedgehog and Beyond --plus multi-targeting cancer inhibitors

Extensive-Stage Small Cell Lung Cancer Phase I
http://clinicaltrials.gov/ct2/show/NCT00927875?term=BMS-83392
The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with carboplatin and etoposide followed by BMS-833923 alone in subjects with extensive-stage Small Cell Lung Cancer (SCLC).

Study Start Date: December 2009
Estimated Study Completion Date: July 2011

Metastatic Gastric, Gastroesophageal, or Esophageal Adenocarcinomas Phase I
http://clinicaltrials.gov/ct2/show/NCT00909402?term=BMS-833923
The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with cisplatin and capecitabine as first-line therapy in subjects with inoperable metastatic gastric, gastroesophageal or esophageal adenocarcinomas.

Study Start Date: November 2009
Estimated Study Completion Date: July 2011

Advanced or Metastatic Cancer Phase I
http://clinicaltrials.gov/ct2/show/NCT00670189?term=BMS-833923
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

Study Start Date: July 2008
Estimated Study Completion Date: April 2011

Multiple Myeloma Phase I
http://clinicaltrials.gov/ct2/show/NCT00884546?term=BMS-833923
To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-833923 administered alone, in combination with lenalidomide plus dexamethasone, or in combination with bortezomib in subjects with relapsed or refractory multiple myeloma.

Study Start Date: July 2009
Estimated Study Completion Date: November 2011


http://clinicaltrials.gov/ct2/results?term=BMS-833923

Information Regarding Safety Profile

Safety Summary
As of October 21, 2009, no patients in the 30, 60, or 120 mg dose cohorts
experienced drug-related ≥ Grade 2 adverse events as defined by the National Cancer
Institute Common Terminology Criteria, Version 3. Two patients experienced drugrelated
Grade 2 adverse events in the 240 mg dose cohort. One patient experienced
hypophosphatemia, and a second patient experienced elevated lipase levels and
pancreatitis which was a serious adverse event.


http://www.exelixis.com/downloads/XL139-A55_EORTC-2009.pdf

CONCLUSIONS
• BMS-833923 is generally well tolerated at 30 mg, 60 mg, and 120 mg
dose levels
• BMS-833923 has a long terminal half-life > 7-days
• BMS-833923 exposures were approximately dose-proportional in the
30-120 mg dose range and greater than dose-proportional (non-linear) at
the 240 mg dose
• A patient with a diagnosis of Basal Cell Nevoid Syndrome (with a known
mutation in PTCH-1) experienced a confirmed PR (240 mg BMS-833923)
– PR continues after the patient’s dose was reduced to 60 mg every
other week and continues on study (128+ days)
– patient continues on study for 128+ days
• BMS-833923 demonstrated pharmacological activity in surrogate tissue at
30 mg, 60 mg, 120 mg, and 240 mg (poster 09-A-483-AACR)