Abstract 6070: Clinical and genomic determinants of PDX engraftment across solid tumors

Abstract Introduction: Patient-derived xenograft (PDX) models support investigation of tumor biology and treatment response, yet determinants of successful engraftment and the extent to which PDXs retain patient tumor genomic features remain incompletely defined. This study evaluated clinical and actionable genomic characteristics associated with PDX establishment across solid tumors. Methods: Tumor specimens from biopsies in 529 patients (555 tumors) were implanted into immunodeficient mice and classified as take or no-take based on successful implantation. Clinical diagnoses and histologic subtypes were recorded. Matched patient tumors and PDXs underwent sequencing to assess mutations, amplifications, deletions, and composite alteration events across actionable genes. Results: Of the 555 implanted tumors, 266 PDXs were generated (∼47% take rate). We generated PDXs from 250 patients across more than 27 tumor types; 14 patients contributed two models, and one contributed three longitudinal models. Pancreatic and esophageal tumors demonstrated higher engraftment frequencies, while peritoneal and appendiceal tumors showed lower frequencies. Among breast cancers, engraftment was higher in triple-negative tumors compared with hormone receptor-positive or HER2-positive subtypes (52% TNBC, 39% HR+, 36% HER2+). Engraftment was more common in tumors bearing TP53 alterations; however, significance was not retained after adjustment for multiple testing (62.6% vs 50.2%; p=0.007, adjusted p=1). Sequencing of 114 PDXs were compared to clinical sequencing in matched patients. Patients harbored alterations in 159 actionable genes; 157 were also detected in PDXs. All PDXs harbored at least one shared actionable alteration, and 36 PDXs retained all actionable alterations present in their matched patient tumor. Additionally, 88 actionable alterations were detected in at least one PDX but not in patients, and 106 PDXs harbored at least one such alteration. All PDXs acquired additional actionable alterations relative to their matched patient tumors. Conclusions: PDX engraftment is feasible from biopsies in advanced cancer; engraftment success varies across tumor types. Sequenced PDXs broadly preserved patient tumor actionable alterations but may also have acquired additional events. Citation Format: Leva Gorji, Kurt W. Evans, Xiaofeng Zheng, Erkan Yuca, Ran Zhang, Hung Le, Gabriela Raso, Argun Akcakanat, Ana Galan Cobo, Timothy P. DiPeri, Milind Javle, Burak Uzunparmak, Funda Meric-Bernstam. Clinical and genomic determinants of PDX engraftment across solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6070.