Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies

Summary

Objectives

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with
fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose
injection, enabling rapid assessment of multiple oncology drugs or drug combinations
simultaneously within a patient's tumor. Tumor responses to cancer treatments are highly
context-specific and often involve complex interactions between the anti-cancer therapy,
genetically diverse tumor cells, and a heterogeneous TME. This complexity is rarely
modeled accurately in preclinical translational models of cancer. By utilizing
intratumoral microdose injections with CIVO in advance of scheduled surgical
intervention, this study will evaluate anti-cancer therapies directly in patients each
with their own unique tumor genomic profile, intact TME, and immune system functional
status. Because the platform delivers microdose amounts of each test agent or combination
directly into the patient's tumor tissue, hypotheses can be tested earlier in the drug
development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance
for Industry.

The CIVO device penetrates solid tumors and simultaneously delivers subtherapeutic
microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents
co-injected with CIVO GLO into discrete regions of the tumor as drug columns. At the time
of the planned surgical intervention (at least four hours to up to seven days after the
CIVO microdose injection), the injected tumor tissue is then excised and tumor responses
are assessed via histological staining of tumor cross-sections sampled perpendicular to
each injection column. Co-injection with CIVO GLO enables identification of each
injection site during resection as well as in tissues stained for analysis. This Phase 0
Master Protocol is aimed at distinguishing promising candidates earlier in the drug
development process while also avoiding systemic toxicities associated with typical
clinical exposures to these therapies.