Clinical trials of active cancer immunotherapy

Active immunotherapy of cancer needs its own clinical trials' methodology. The standard methodology paradigm for clinical trials in oncology was developed for cytotoxic drugs, which differ dramatically from cancer vaccines in their mode of action and toxicity profile. To minimize the risk of overlooking benefits for patients, Mackiewicz and Nawrocki invite to open discussion on vaccine trials' methodology. Our point of view is based on several Phase I and II trials with hundreds of melanoma patients treated with allogenic cellular vaccine genetically modified with cytokine genes. We feel that a simplified two-stage clinical trial design without a separate Phase I is justified. In the first stage, preliminary efficacy together with proof-of-principle and feasibility issues could be addressed. For real efficacy assessment, careful consideration of end points is necessary. Immunologic responses and objective clinical responses are not the best measures of vaccine efficacy for many patients who benefit from treatment. Randomized single institution studies with time-to-event end points are probably well suited for such combined Phase I/II studies. In the second stage trial (Phase III), the final efficacy analysis with comparator arm is needed.