A report recently published in Clinical Cancer Research by Dr. Samir Khleif along with colleagues from the University of Virginia and the National Cancer Institute addresses the FDA’s recognition of a needed paradigm shift in the approach to cancer vaccine development. Since the mechanism of action of cancer vaccines is distinct from that for cytotoxic agents, the applicability of the traditional phase I dose escalation design to identify a maximum tolerated dose or biologically active dose has been questioned.
This report presents the first evidence-based support for a new approach to conducting first-in-man cancer vaccine clinical trials. Through a retrospective analysis of 239 phase 1, phase 1/2, and pilot therapeutic cancer vaccine studies published from 1990 to 2011 (4,952 patients), the researchers discovered little to no correlation between therapeutic cancer vaccines and risk of serious toxicities; likewise, toxicities did not correspond with dosage.
Their proposed new design tool identifies a dosage that is safe and immune-active, eliminates the need to enroll large numbers of patients for trials using non-toxic vaccines, and permits the addition of other agents to boost vaccine efficacy.
[Rahma OE, Gammoh E, Simon R, Khleif SN. Is the “3+3” dose escalation phase 1 clinical trial design suitable for therapeutic cancer vaccine development? A recommendation for alternative design. Clin Cancer Res. 2014 Jul 18. pii: clincanres.2671.2013. [Epub ahead of print]]