Abstract 5177: Ex vivo assessment of cellular mass response predicts clinical efficacy in solid tumors

Abstract Introduction: Identifying personalized, efficacious therapies for cancer remains an urgent unmet need in oncology. While genomics-based biomarkers have demonstrated significant progress, they are not universally applicable, with most patients still treated using clinical guidelines. Experimental procedures: We have previously demonstrated broad clinical applicability of a functional precision medicine (FPM) workflow that incorporates high-resolution measurements of single-cell mass changes in response to drugs. As a highly integrative biomarker of cellular state, mass change serves as a rapid and mechanism agnostic readout of drug response, demonstrating an ability to detect signal from over 100 different cytotoxic and targeted therapies within 24 hours of treatment ex vivo. As a single-cell assay that requires as few as 10,000 cells to assess drug response, this method does not require any ex vivo culture for cell expansion and is compatible with a range of clinically relevant tissue specimen formats. Together, these features have enabled this mass response framework to be implemented in a CLIA-certified laboratory with a reporting turnaround time of just two days. Summary of the new, unpublished data: Having previously shown that mass response testing is compatible with various solid tumor specimen formats such as malignant fluids, core biopsies and fine needle aspirates, here we present preliminary results that demonstrate compatibility with surgically resected tissue specimens. Specifically, we demonstrate that mass response testing results correlate with clinical response across of broad array of solid tumors. In our cohort of 24 patients, we found that mass response measurements correlated with clinical response to therapy with an accuracy of 83% (OR=19.66, P=0.003). Within this group, we also found clear examples of how mass response testing can serve as a valuable complement to existing genomic approaches to guide therapy. Importantly, we demonstrate both concordant and discrepant results using small molecule inhibitors in the setting of known biomarkers of response, highlighting the need for functional testing in precision cancer medicine. Conclusions: These results support that mass response testing is feasible and broadly applicable to solid tumor malignancies and may serve as a valuable complementary readout for informing therapeutic selection for cancer patients. Citation Format: Robert Kimmerling, Mark Stevens, Selim Olcum, Madeleine Vacha, Rachel LaBella, Katie Katsis, Reginald Aikens, Cathleen Hannah, Audrey Guo, Juanita Fujii, Zayna Shaheen, Srividya Sundaresan, Ashley Rainey, Andrew M. Blakely, Jonathan Hernandez, Anobel Tamrazi, Clifford Reid. Ex vivo assessment of cellular mass response predicts clinical efficacy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5177.