AVATAR: Efficacy of personalized tumorogram-based therapy in breast cancer established from patient-derived organoids.

TPS1157 Background: Despite therapeutic advances in advanced breast cancer (ABC), predicting drug efficacy for individual patients remains difficult. Patient-derived tumor organoids (PDTOs) could enable drug efficacy testing within a timeframe compatible with clinical decision-making. We hypothesize that personalized treatment based on PDTO-guided tumorograms can improve outcomes for patients with HER2-negative ABC. Methods: AVATAR (NCT06459791) is a single-arm multicenter phase II trial assessing tumor response rate within 6 months as the primary endpoint in patients with HER2-negative ABC treated with tumorogram-guided chemotherapy. A biopsy of a tumor lesion is performed and transferred to the laboratory for PDTO establishment. While waiting for the result of the tumorogram, the patient receives standard-of-care treatment. A drug screening of standard-of-care drugs is performed on the PDTO (~5-10 drugs per patient), with selection adapted to the clinical setting. A multidisciplinary team makes therapeutic recommendations based on the tumorogram. A tumorogram is considered informative if it identifies at least one chemotherapy drug that is considered effective in the PDTO model. When possible, patients with an informative tumorogram receive one of the recommended treatments as their next line of therapy. Otherwise, they receive standard treatment. Eligible patients include those with HER2-negative ABC who are treated with chemotherapy (endocrine-resistant for HR+/HER2-), have a performance status of 0-1, and have a tumor lesion that can be biopsied. Patients who have received more than three lines of chemotherapy in the metastatic setting or who have progressive brain or leptomeningeal metastases are excluded. We hypothesize that the prescription of chemotherapy based on an informative tumorogram will be clinically meaningful if the tumor response rate is at least 25% (p0). With a one-sided α of 9%, a power of 90%, and an alternative hypothesis of 45% (p1), 39 patients should be treated according to an informative tumorogram, and 110 patients need to be included (assuming a minimum of 40% informative tumorograms and accounting for dropouts). Enrollment began in December 2024 and is ongoing. Clinical trial information: NCT06459791 .