Predicting success in regulatory approval from Phase i results

Purpose: Drug development in oncology is resource intensive and has a high failure rate. In this exploratory analysis, we aimed to identify the characteristics and outcomes of published Phase I studies associated with future Food and Drug Administration (FDA) approval. Methods: Phase I studies of approved and non-approved anticancer agents between 2000 and 2013 were retrospectively examined. Fisher's exact and chi-squared tests were used to compare the potential predictive measures. Results: Phase I studies of 88 anticancer agents (54 approved and 34 non-approved by the FDA), treating a total of 4,423 subjects, were examined. The median number of patients in Phase I trials of approved and non-approved agents was 44.5 and 32, respectively. A total of 423 subjects (86 reporting studies) had a complete responses, and 342 subjects (80 reporting studies) had a partial responses (PR). A higher number of PR (P < 0.001), PR rate (P = 0.003) and longer PR duration (P = 0.001) were predictive of regulatory success. Conclusions: These preliminary findings indicate that objective responses in Phase I trials may have predictive value for later regulatory approval.