Abstract 815: AZD5335, a folate receptor alpha-targeted ADC, enhances ovarian cancer treatment with bevacizumab, paclitaxel and/or carboplatin

Abstract Elevated expression of folate receptor alpha (FRα) in various cancers, including epithelial ovarian cancer (EOC), highlights FRα as a potential target for the development of novel therapeutics to treat FRα-expressing tumor types. AZD5335, an FRα-targeting antibody conjugated to a topoisomerase 1 inhibitor (TOP1i) payload, is currently being investigated in the FONTANA Phase I/IIa clinical trial (NCT#05797168), either as a single agent or in combination with a PARP1-selective inhibitor (saruparib). Using an FRα-expressing EOC xenograft model (OV90), we evaluate additional AZD5335-relevant combined treatment strategies and report pre-clinical assessment of AZD5335 in combination with bevacizumab, paclitaxel and/or carboplatin. Compared to monotherapy treatment, we successfully demonstrate that combination treatments with AZD5335+bevacizumab, AZD5335+paclitaxel or AZD5335+carboplatin result in significant and durable anti-tumor responses. Using the same EOC xenograft model, we extended these studies to include AZD5335+bevacizumab plus either paclitaxel or carboplatin treatments and demonstrated that these triplet combos resulted in superior and durable anti-tumor activities. Combination data in a number of additional CDX/PDX will be presented. A series of in vitro studies will also define the ADC/SOC drug interactions and further delineate underlying mechanisms driving enhanced efficacy. These studies inform our ongoing clinical development of AZD5335 in ovarian cancer. Citation Format: Jason J. Zoeller, Ravinder Tammali, Ana De Almeida, Shane Cronin, Nancy Lee, Alma Andoni, Claire Myers, Elaine Joseph, Michael Lehmann, Rebecca Sargeant, Ina Bisha, Simon Christ, Iris Dino, Xhenifer Guza, Jixin Wang, Lisa Godfrey, Roger Dodd, Neki Patel, Edward Rosfjord, Marco Gymnopoulos, Tim Brier, Sabina Cosulich, Elaine Hurt, Puja Sapra. AZD5335, a folate receptor alpha-targeted ADC, enhances ovarian cancer treatment with bevacizumab, paclitaxel and/or carboplatin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 815.