Download File - JOHN J. HADDAD, Ph.D.

178 Bot and Obrocea
types at maximum, via a set of randomized trials carried out in parallel. This
approach would achieve a faster evaluation, in an objective fashion, of the efficacy
of the cancer vaccine as opposed to using historical controls (a usual source for
bias in the case of first–in-class investigational drugs). If used properly, this
approach may prevent transition to phase 3 if the drug is not likely to be effective;
conversely, this strategy may offer significant information and even anticipate the
optimal design of the phase 3 program. In addition, due to the fact that cancer
vaccines can be applied as adjuvants in minimal residual disease post-standard
therapy, they can be used as a companion to standard therapy (combination
approach) or in late stages, in refractory setting as monotherapy. Ideally, all these
indications should be explored in parallel in a randomized phase 2b program to
provide a data set to make appropriate recommendations for one or multiple
pivotal phase 3 trials necessary for defining the product profile and registration.
CONCLUSIONS
In conclusion, due to cancer vaccines’ intrinsic nature (targeted therapies with
indirect MOA) and scarcity of benchmarks in terms of late-stage or approved
products, a re-designed translational approach would be fully beneficial for the
development of such therapies. The critical element of this approach is the
stratified medicine concept—essentially encompassing biomarker-guided R&D.
This approach can be done through an iterative translational strategy aimed to
optimize the investigational drug and define the target population prior to
randomized trials. In addition, innovative, flexible, and adaptive clinical trial
designs will support early generation of relevant data in humans. While there are
differences in between technology platforms explored as cancer vaccines, these
principles apply irrespectively and should result in an increased likelihood of
success. To extract the essence of R&D in the post–human genome project era of
molecular targeted approaches, we no longer develop drugs alone but also
therapeutic approaches, encompassing both the means to identify the patient and
the appropriate medicament.
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