ABSTRACT
Prostate cancer, rather indolent by nature, has specific subtypes present with aggressive locoregional disease
that are quickly becoming hormonal resistant. Patients with castrate-resistant disease (CRPC) are generally
younger and non-Caucasian, and many suffer from local progression, edema, and pain. Radiotherapy (RT) is
offered but limited by the extent, former exposure, and resistance of disease. Sequential multiple chemotherapy
or RT treatments, offered as standard of care, are hard to comply to, especially in low-resource populations.
Treatment of this symptomatic population is often terminated prematurely, or never started, due to financial and
time restrictions. Innovative, shorter more efficient treatments are needed, especially to reduce disparities in
compliance and outcomes of global cancer care.
In extensive preclinical work, the combination of RT with immunogenic smart radiotherapy materials (iSRBs),
addressed as radio-immunotherapy dose-painting (RAID) technology, brings intra-tumoral slow-release
antiCD40 payload in the target that gets irradiated and has shown to prime the immune system and create
sustainable tumor control by in situ-vaccination, even after different therapeutic options have failed. Moreover,
this combination treatment can improve quality of life (QoL) fast by a short simple intervention with fewer side
effects, having an antiCD40 payload far smaller than needed in intravenous (IV) immunotherapy.
The overall goal of this project - proposed by Nanocan Therapeutics Corporation in collaboration with John
Hopkins Medicine, Dana-Farber Cancer Institute and Northwell Health - is to bridge preclinical work to the first
clinical trial with the innovative RAID technology and confirm its potential for in situ-vaccination that can extend
the use of radiotherapy (RT) from palliative local treatment to systemic disease control in one session.
The iSRBs are as seed-like fiducial markers administered directly in the prostate tumor by ultrasound guided
needles. The iSRBs create contrast on CT and KV imaging making RT set-up fast; iSRBs slowly release (20mcg
per unit over 15 days) anti-CD40 payload directly the target which gets irradiated, triggering in situ-vaccination.
The purpose of this project is to translate extensive safety and efficacy data from small animal studies of single
fraction RT combined with slow released intra-tumoral antiCD40 delivery to a first human trial for CRPC patients.
The first part will be used to optimize iSRBs into a cGMP product, and confirmation of larger volume testing in
monkeys to confirm safety, immunogenicity, and pharmacokinetics already performed in extensive small animal
work. Milestones will complete IND filling by Nanocan Therapeutics. After FDA approval, second part of the
project will encompass the Phase 1 single arm open label clinical trial seeking confirmation of safety and number
of iSRBs as well as RT dose needed in CRPR patients. This project can provide all needed data for planned
Phase II clinical work in aims offering a novel treatment paradigm for CRPR patients.