The US Food and Drug Administration (FDA) has published draft guidance on designing clinical trials for therapeutic cancer vaccines that will support a licence application to the agency’s Center for Biologics Evaluation and Research (CBER).

The draft guidance acknowledges the “different considerations” presented by cancer vaccine development compared with designing trials for traditional cytotoxic drugs or biological products for oncology indications.

For example, it notes, the “course of antigen presentation and processing, activation of lymphocytes, and tumour cell killing, is expected to require a considerable time in vivo, especially if vaccination requires several doses”.

The document looks at the key clinical considerations spanning both early-phase (defined as Phases I and II) and late-phase (Phase III) clinical trials of therapeutic cancer vaccines, such as the relevant patient population (including disease setting, tumour heterogeneity and co-development of cancer vaccines with tests for the targeted antigen); monitoring the immune response; and disease progression/recurrence immediately or shortly after initial administration of the vaccine.

Specific considerations for early-phase trials of therapeutic cancer vaccines include the starting dose and dosing schedule; dose escalation; and single-arm versus randomised Phase III trials. The section on late-phase trials covers the vaccine’s safety profile from early-phase development; endpoints for product licensing; superiority versus non-inferiority designs; control issues; delayed vaccine effects; trials of autologous cancer vaccines derived from the patient’s own tumour; and accelerated approval regulations.

The draft guidance also addresses the issue of concomitant therapies that may diminish or enhance the ultimate therapeutic effect of a cancer vaccine, recognising that one of “the recent advances in the immunotherapy field is the realisation that effective destruction of a tumour involves multiple coordinated immune mechanisms”.

The FDA’s draft guidance for industry on Clinical Considerations for Therapeutic Cancer Vaccines is open for comments until 17 December 2009. It can be accessed online at: www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm182443.htm.