Leveraging Early Biomarker Data to Assess Futility in an Oncology Test-of-Concept Study

• Activity Number: 300
• Type: Contributed
• Date/Time: Tuesday, July 31, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Robin Mogg*+ and Devan Mehrotra
• Companies: Merck Research Laboratories and Merck Research Laboratories
• Keywords: biomarker ; conditional power ; futility analysis ; oncology ; test of concept study

Abstract

Early reductions in tumor volume (e.g., 6 weeks after initiating treatment) may be associated with longer survival endpoints in advanced metastatic colorectal cancer. We explore using this biomarker in combination with accrued survival data to assess futility in a slowly enrolling, controlled Phase 2a test-of-concept study for a highly selective population of colorectal cancer patients. The futility analysis is planned when ~50% of patients enrolled have biomarker information, at which time the expected survival event rate is ~50% of the total event rate. We propose leveraging the observed association between biomarker and survival at the time of the futility analysis to help predict survival times in patients without an event. Conditional power to reject the null hypothesis at the end of the study is used for the futility assessment. We assess the utility of incorporating early biomarker information for futility decisions under a variety of settings via simulation.