Abstract A011: An implantable microdevice to interrogate responses to therapy in ovarian cancer
Authors: Stover Elizabeth H. , Tatarova Zuzana , Bhagavatula Sharath K. , Dominas Christine , Polak Madeline , Rabbitt Alexis , Gardner Jeanette , MacNeill Kim , Azzolini Natalie , Ahn Sebastian , Worley Michael J. , Elias Kevin M. , Kolin David L. , Liu Joyce F. , Matulonis Ursula A. , Silverman Stuart G. , Horowitz Neil S. , Jonas Oliver 
Published: March 2024

Abstract
The selection of optimal therapies for ovarian cancer patients, especially in the recurrent setting, is hindered by a lack of biomarkers that predict responsiveness to specific treatments. An implantable microdevice (IMD) is a new technology to evaluate in situ drug responses in cancer. The IMD is 750 microns wide and 6 mm long, and it is implanted into tumors using a percutaneous delivery needle under imaging guidance. Multiple reservoirs within the device release microdoses of up to 20 drugs or drug combinations into non-overlapping regions of tumor. After 24-72 hours, the IMD and surrounding tumor are then removed via surgery, and the tumor tissue is analyzed to evaluate drug effects. The IMD enables efficient assessment of multiple drugs and combinations in parallel. Drug effects are evaluated in situ within the tumor, providing information on the tumor microenvironment as well as cancer cells. A variety of assays - including protein immunofluorescence for markers of apoptosis, proliferation, or signaling pathways - can be performed on the tumor tissue adjacent to the IMD to evaluate drug effects. We previously tested the IMD in patient-derived xenograft models of ovarian cancer and showed that the responses to different drugs (standard and experimental) can be evaluated in ovarian tumors. Currently, we are conducting a phase I clinical trial (NCT04701645) in ovarian cancer patients undergoing standard-of-care surgery to test the safety and feasibility of IMDs in ovarian cancer. One to four IMDs, each containing 16 standard-of-care agents plus controls, are implanted percutaneously under CT guidance into a single tumor site ~24 hours prior to surgery. A CT scan is repeated before surgery to confirm the devices’ locations. The IMDs with the surrounding tumor tissue are removed at surgery and fixed for analysis. Patients are evaluated for safety endpoints during and after the IMD placement and retrieval. As of July 2023, two patients have undergone successful IMD placement and tissue analyses. No adverse events due to the IMD have occurred. In terms of feasibility, both patients had tumor tissue that was evaluable for drug responses. We have applied cyclic immunofluorescence on ovarian tumor tissue to evaluate protein responses to the drugs in the microdevices. Preliminary data indicates that the different drugs vary in the extent of cell death induction and changes in proliferation and may have specific effects on the tumor microenvironment. Ongoing analyses will examine the changes in protein biomarkers for DNA damage repair, key ovarian cancer signaling pathways, and immune and stromal cells within the tissue in drug-treated areas compared to control regions. In summary, we propose that an IMD may be a clinically tractable approach to evaluating tumor responses to multiple drugs within patient tumors. IMDs may have both research and clinical applications to improve the selection of effective drug treatments in patients with ovarian cancer.
Citation Format: Elizabeth H. Stover, Zuzana Tatarova, Sharath K. Bhagavatula, Christine Dominas, Madeline Polak, Alexis Rabbitt, Jeanette Gardner, Kim MacNeill, Natalie Azzolini, Sebastian Ahn, Michael J. Worley Jr., Kevin M. Elias, David L. Kolin, Joyce F. Liu, Ursula A. Matulonis, Stuart G. Silverman, Neil S. Horowitz, Oliver Jonas. An implantable microdevice to interrogate responses to therapy in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A011.