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

Development of Novel Immunotherapeutics 153
both preclinical toxicology strategy and the design and identification of end points
in clinical trials. Altogether, these characteristics define critical gaps in the
development of cancer vaccines: (1) between preclinical development and clinical
exploration due to the complexity of MOA and limited predictability of most
preclinical models and (2) between early- and late-stage clinical development due
to the scarcity of PD and surrogate end points to guide to development process.
REDESIGNED R&D STRATEGY IN SUPPORT OF “CANCER VACCINES”
To meet these challenges and aim for an appropriate testing of proof of concept,
as well as identification of optimal candidates for randomized proof of concept
trials, one needs to consider different approaches of development for active
immunotherapies in cancer versus drugs with a more direct MOA.
First and foremost, to bridge the gap between preclinical exploration and
clinical evaluation, we need to abandon the classical linear development process
and instead factor in the complementary value of data gathered in preclinical and
clinical models in support of selecting the right lead candidate. This selection
will have a profound outcome on the development process, for example, from
design, optimization, and preclinical exploration to Investigational new drug
application (IND)-enabling studies followed by proof of concept trials and
finally, confirmatory phase 3 trials. Essentially, this will translate into a two-way
approach—bench to bed and reverse—aiming to ensure optimization of the
therapeutic candidate (composition, regimen, tumor type, and indication) prior to
initiating larger randomized trials (Fig. 2).
Figure 2 A comparison between linear and cyclical development paths of second generation
(A) or first in class (B) investigational compounds.