An alternative clinical trial design for early cancer vaccine development to phase 3+3 design.

2578 Background: Traditional phase I, “3+3 dose escalation” design, is conducted to identify the MTD and in some cases the optimal biologic dose. Given their unique mechanism of action and the profile of their clinical outcome, this design may not apply to cancer vaccines. The therapeutic cancer vaccine FDA guidance calls for an alternative early development design. Nevertheless, whether an alternative design should be based on “dose escalation” is still an opened question. Methods: We analyzed the toxicity profile in 241 phase 1, 1/2 and pilot therapeutic cancer vaccine trials conducted between 1990 and 2011. Results: Sixty-two grade 3/4 vaccine related systemic toxicities were reported in 4952 treated patients (1.25 events/100 patients). Interestingly, only 2 out of 127 trials that used dose escalation reported vaccine related DLTs, both trials used bacterial vectors. Furthermore, correlation of immunological response with dose level showed no consistent trend. Conclusions: Our analysis suggests that in...