Vaccine 25S (2007) B97–B109 Review Lessons from randomized phase III studies with active cancer immunotherapies – Outcomes from the 2006 Meeting of the Cancer Vaccine Consortium (CVC) Lothar H. Finke a,g,* , Kerry Wentworth b,g , Brent Blumenstein c , Natalie S. Rudolph d , Hyam Levitsky e,g , Axel Hoos f,g a Argos Therapeutics, Inc., Durham, NC, USA b Antigenics, Inc., New York, NY, USA c TriArc Consulting, Seattle, WA, USA d Rudolph Biomedical Consulting, Boylston, MA, USA e Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Johns Hopkins University School of Medicine, Baltimore, MD, USA f Bristol-Myers Squibb Company, Wallingford,CT, USA g Cancer Vaccine Consortium (CVC), Mt. Laurel, NJ, USA Received 16 April 2007; received in revised form 1 June 2007; accepted 14 June 2007 Abstract After years of effort to develop active cancer immunotherapies, seven candidate products achieved promising results in phase I/II studies that triggered phase III randomized studies. One candidate to date has received an approvable letter from the United States Food and Drug Administration (FDA), defining a clear path to licensure for sipuleucel-T (Provenge ® , Dendreon) within the next couple of years. The other phase III studies failed to achieve statistical criteria for some or all of the critical endpoints. Yet, there is widespread recognition that using a patient’s own immune system to target and destroy cancer cells may offer an effective biological therapy with less toxicity than presently available anti-cancer therapies, and several candidates are still being evaluated in clinical studies. This review summarizes the lessons learned from these case studies, evaluates scientific, study design, and business factors that can affect study outcomes, identifies common challenges faced by sponsors developing these innovative therapies, and provides considerations for future study designs that may increase the likelihood of success. © 2007 Elsevier Ltd. All rights reserved. Keywords: Active cancer immunotherapy; Phase III clinical studies; Lessons; Development paradigm Contents 1. Introduction ....................................................................................................... B98 2. Case studies ....................................................................................................... B99 2.1. Melacine ® ................................................................................................... B99 2.1.1. Product and therapeutic principle ...................................................................... B99 2.1.2. Phase I/II results ..................................................................................... B99 2.1.3. Phase III design ...................................................................................... B99 2.1.4. Phase III results ...................................................................................... B99 * Corresponding author at: Argos Therapeutics, Inc., 4233 Technology Dr., Durham, NC 27704, USA. Tel.: +1 919 287 3421; fax: +1 919 827 4892. E-mail address: lfinke@argostherapeutics.com (L.H. Finke). 0264-410X/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2007.06.067