Title:Defining and Managing Expectations for Early Immunotherapy Cancer Trials
VOLUME: 10 ISSUE: 1
Author(s):Thomas Kieber-Emmons, Angela Pennisi, Anna Lane, Eric Siegel, Martin Cannon, Behjatolah Monzavi-Karbassi and Issam Makhoul
Affiliation:Department of Pathology, University of Arkansas for Medical Sciences and the Winthrop P. Rockefeller Cancer Institute. 4301 West Markham St., #824, Little Rock AR 72205 USA.
Keywords:Cancer clinical trial, Clinical benefit, Early phase trial design, Efficacy, Immunotherapy, Monoclonal Antibody,
Vaccine.
Abstract:This review discusses the concept of expectations in assessing direct benefit to participants
in phase I immunotherapy studies. With the push toward a faster assessment of clinical benefit or efficacy,
limiting phase I studies to safety determination only is now viewed as obsolete and has been replaced
by designs that draw attention to therapeutic benefit or efficacy. While this approach is touted
as being more flexible in trial conduct, these designs are particularly problematic for immunotherapy
studies. Defining and managing expectations is paramount on understanding the key axioms that
emerge that include i) understanding bias in models and mechanistic results, ii) that no test is perfect,
iii) it is difficult to select a good predictive biomarker in the absence of clinical data, even for targeted
therapies, iv) markers predictive for monotherapy may not be predictive for combination therapy, and v) all about improved
patient selection. Considering the heterogeneity of cancers and the immune response of the host, we think that
immunotherapy should be developed in parallel with the identification of different clinico-pathological models of immune
response to cancer. This approach would accomplish two important goals: 1) provide a biological understanding of the
complete in vivo environment, thereby giving investigators the opportunity to optimize and maximize the effect of a specific
immunotherapy agent and 2) addressing host environment issues simultaneously so that safety data and perceived
benefit can be achieved more quickly.
