Development of a multifunctional interventional device for biopsy and optical imaging-based phase-0 drug response measurements

About This Grant

PROJECT SUMMARY: Background. Traditional drug development is slow, costly, and inefficient, with over 90% of drugs failing in clinical trials. Personalized medicine also faces challenges in accurately matching patients with optimal treatments. "Phase-0" microdosing, involving the delivery of tiny drug doses directly into target tissues, has the potential to transform both drug development and personalized drug selection by directly evaluating drug effects in patients without systemic toxicity and rapidly identifying the best treatment for each individual. Our team is leading the clinical translation of an implantable microdevice (IMD) that provides Phase-0 microdose readouts of multiple drugs in a single patient. IMDs are placed into diseased tissue (most commonly tumors) and subsequently release drugs into spatially discrete microscopic regions. The devices and surrounding tissue are then removed surgically and drug effects are characterized and compared using a multi-omic spatial analysis pipeline. Preclinical and first-in-human IMD trials have been highly promising with unprecedented drug insights. However, surgical resection required for IMD analysis is not feasible or safe in most deep anatomic locations. This has prevented IMD validation and use in most settings where they are needed, including neoadjuvant and aggressive metastatic cancer. A less invasive and safer approach is needed to enable broad clinical application. More specifically, there is a critical and currently unmet need for a nonsurgical interventional device to deliver drug microdoses and subsequently biopsy drug-containing tissues for Phase-0 measurements. Proposal and impact. In Aim 1, we will develop an interventional drug response assay (IDRA) device that will broadly enable biopsy-based Phase-0 measurements from any percutaneously accessible site similar to routine percutaneous biopsies, with similar outpatient workflow and low risk. In Aim 2, we will validate IDRA safety and feasibility in prostate and ovarian cancer pre-clinical models (Aim 2). This will enable clinical investigational trials in neoadjuvant and advanced metastatic prostate and ovarian cancer, two settings where oncologists have expressed a critical and urgent need. In a parallel Aim 3, we will integrate label-free optical imaging into the IDRA and evaluate feasibility to image real-time drug effects directly in tumors (Aim 3). Aim 3 will lay the groundwork for our long-term goal of dynamic in-vivo optical Phase-0 imaging, which would provide unprecedented capability to directly monitor drug response and resistance over time. In the long term, these aims have the potential to broadly transform drug development and personalized treatment selection in diseases throughout the body.