29 Pilot study of an implantable microdevice forin vivo evaluation of drug response in renal cell carcinoma (NCT05700461)

Abstract Background There are multiple therapies for renal cell carcinoma (RCC), yet no personalized biomarkers exist that can guide optimal treatment for individual patients. We developed implantable microdevices (IMD) that can be placed within a target tumor using a standard small-gauge interventional needle under imaging guidance. The IMDs deliver spatially segregated microdoses of up to 20 different drugs and/or combinations over multiple days, and then are retrieved surgically with surrounding tissue. This allows for the assessment of tumor response to multiple drugs in vivo within the native tumor microenvironment, without exposing the patient to systemic drug toxicity. We are conducting a trial to evaluate the safety and feasibility of IMD implantation in RCC tumors and subsequent collection of drug response data on targeted, cytotoxic, and immune-modulatory agents. Methods Eligible patients have suspected or confirmed RCC and are planned for standard surgical resection of either their primary tumor or metastasis. Three days prior to surgery, one or more IMDs are implanted percutaneously into the tumor under CT guidance. Following nephrectomy or excision of a metastasis, the microdevices with surrounding tumor are removed en bloc; subsequently, the tissue is fixed, embedded and sectioned. The tumor/IMD cross-sections are analyzed for drug effect for each of the spatially separate treatment effects using a wide range of techniques, including immunohistochemistry for proliferation and pathway markers, spatial immune profiling using a panel of 25 tumor microenvironment markers, and spatial transcriptomics. Patients receive subsequent standard of care systemic treatment as per their oncologist’s discretion. Five patients have been enrolled and a total of 16 IMDs have been implanted to date. Enrollment is ongoing for a planned total of 20 patients. Success is defined as meeting both safety and feasibility endpoints. Safety is defined as two or fewer safety failures out of 20 enrolled patients. Feasibility is defined as 16 or more patients with successful microdevice implantation and retrieval of interpretable data. IMDs will be analyzed to explore spatially segregated drug effects on the tumor microenvironment including tumor cell death and immune cell activation, as well as evidence of differential tumor drug sensitivity across treatments and patients. Conclusions Implantation of microdevices in RCC tumors may be a useful approach to improve treatment selection and accelerate drug development. Trial enrollment is ongoing.