Abstract B012: Clinical trial of an implantable microdevice to evaluate drug responses in ovarian cancer

Abstract The selection of optimal therapies for patients with ovarian cancer is difficult, especially in recurrent disease. An implantable microdevice (IMD) is a new technology to evaluate in situ drug responses in cancer. An IMD, about the size of a grain of rice, is implanted into human or murine solid tumors and releases microdoses of up to 20 compounds in spatially distinct regions of the tumor. Histologic analysis of tissue surrounding the IMD is used to quantitate tumor response. Using IMDs, we can measure tumor sensitivity to multiple drugs or drug combinations in parallel, directly in the tumor with its native microenvironment. Previous studies showed that measurement of local drug response with IMDs in solid tumors correlates with systemic drug response in animal models. We are conducting a clinical trial (NCT04701645) to evaluate the safety and feasibility of IMD implantation in patients with ovarian cancer undergoing surgical resection for clinical indications. Several IMDs, each with 16 standard-of-care drugs and controls, are implanted into a tumor 24-72 hours prior to surgery using a percutaneous delivery needle under CT guidance. After the mass is resected, the tumor tissue containing the IMDs is formalin-fixed, sectioned, and stained to evaluate cellular responses to drug treatment. The aim of the trial is to assess the safety and the feasibility of IMDs in ovarian cancer. Four patients have enrolled to date (histologies: 2 high-grade serous, 1 clear cell, 1 granulosa cell) with 3-4 IMDs implanted per patient. No adverse events attributable to the IND were observed. Of 14 total devices, 10 provided evaluable histology information (4 were dislodged from the tumor ex vivo during pathology processing). Several assays are being applied to evaluate the effects of each drug on the tumor tissue, including 1) immunohistochemistry for apoptosis (cleaved caspase 3, CC3); 2) cyclic immunofluorescence for protein markers; 3) spatial transcriptomics. Regions of interest are selected adjacent to each drug reservoir, and imaging methods quantitate different cell types and markers of drug response. Initial results from three patients demonstrate moderate induction of apoptosis via CC3 staining with a subset of drugs, but minimal CC3 staining for other drugs, in each patient’s tumor. Cyclic immunofluorescence staining is completed on tissue from the first two patients, and a spatial transcriptomics panel is completed on tissue from one patient, both technically successful, and data analysis is ongoing. Additional patients are being enrolled to the clinical trial. In summary, our clinical trial experience indicates that IMDs are safe to implant into tumors of patients with ovarian cancer and that it is feasible to retrieve the IMDs after surgery and obtain informative measurements of mRNA and protein responses in ovarian cancers exposed to different drugs. IMDs may represent an effective new technology for functional precision medicine in ovarian cancer. Citation Format: Elizabeth H. Stover, Sharath K. Bhagavatula, Christine A. Dominas, Sebastian W. Ahn, Samantha E. Martin, David L. Kolin, Michelle S. Hirsch, Madeline Polak, Alexis Rabbitt, Jeanette Gardner, Kimberley MacNeill, Zuzana Tatarova, Michael Worley Jr., Kevin M. Elias, Joyce F. Liu, Ursula A. Matulonis, Stuart G. Silverman, Neil S. Horowitz, Oliver Jonas. Clinical trial of an implantable microdevice to evaluate drug responses in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B012.