Predicting Successful Phase Advancement and Regulatory Approval in Multiple Myeloma From Phase I Overall Response Rates

PurposeDrug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval.Patients and MethodsSeventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval.ResultsThe median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I tria...