Introduction: More than 150,000 women die worldwide every year of Triple-Negative Breast Cancer (TNBC). There are a range of treatment options, but no good way to match patients to their optimal treatment. For most newly diagnosed patients with early TNBC, the current standard of care is neoadjuvant chemo/immunotherapy before surgery, with patients who achieve a pathological complete response (pCR) having a better prognosis. We have developed a Functional Precision Medicine (FPM) test that uses a fresh biopsy, dissociates the cells, embeds them in a 3D hydrogel matrix, cultures them in a microfluidics device and tests them against a range of systemic therapies, while using a computer vision pipeline to measure responses to therapies ex vivo. Methods: We designed and conducted an observational multi-centre clinical trial to assess the feasibility of using our FPM assay in patients with newly diagnosed TNBC undergoing neoadjuvant therapy. Patients underwent an additional core needle biopsy followed by systemic therapy as part of routine care. We assessed the response in our assay against whether patients achieved pCR or not at the time of definitive surgery, and calculated Receiver-Operating Characteristic curves (ROC) to optimize cut-offs. In patients who did not achieve pCR, we explored whether there were other regimens that had a better in-assay performance. Results: In cohort A, we recruited 34 patients, of whom 12 are evaluable as of August 2024. All were female. Nine patients achieved a pCR. The AUC for the ROC for predicting pCR vs. non-pCR was 0.78. In the 3 patients who did not achieve a pCR, one patient had a regimen that performed better in assay than the treatment they received, and where the response was greater than the cut-off that predicted pCR in other patients. Conclusion: We have presented interim results from a novel FPM assay in patients with early stage TNBC. Our test demonstrates good performance in predicting pCR. The trial continues to accrue data, and Cohort B continues to recruit (PEAR-TNBC; NCT05435352).

Williams, Peerani, Tham, Iori, de Fraine, Loughrey, Kaffa, Richardson, Liberal, Velentza-Almpani, Wiskerke, Sangkolah, Crawley, Kearney, Bah, Ranatunga are employees of Pear Bio, with salary, stock options and IP. Hall has received honoraria from Pfizer, Eisai, MSD, Seagen, Exact Sciences, Gilead, AstraZeneca and conference expenses from Lilly and Novartis. Tasoulis has received honoraria from the BMJ and Company: BMJ and IntegraConnect Kirwan reports no Conflict of Interest

NCT05435352

https://www.clinicaltrials.gov/study/NCT05435352

This study was funded by Ourotech (trading as Pear Bio)

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London Queen Square Research Ethics Committee gave ethical approval for this work. Reference: 21/PR/1027

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