Bivariate Continual Reassessment Method (BCRM) Applied to Oncology Dose Escalation Study

• Activity Number: 31
• Type: Contributed
• Date/Time: Sunday, August 4, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yinghua (Grace) Zhang*+ and Jie Ding
• Companies: GSK and GSK
• Keywords: BCRM ; CRM ; dose escalation ; oncology ; monoclonal antibody

Abstract

The traditional dose escalation study in Oncology based solely on toxicity and without regard to the drug's efficacy. We propose extending the continual reassessment method (CRM) to a bivariate study design which the optimal dose recommended to expansion cohort is based jointly on both toxicity and efficacy. We call this study design Bivariate Continual Reassessment Method (BCRM) and demonstrate through simulation the BCRM has excellent operation characteristics compared to the traditional dose escalation study. We also demonstrate the BCRM will have potential wide application to monoclonal antibodies in Oncology when the therapeutic window is much lower than the maximum tolerated dose (MTD) or MTD cannot be reached practically.