Abstract PO5-27-10: Next generation antibody drug conjugates: Multi-payload conjugates targeting multiple mechanisms of cell killing

Abstract Background: ADCs have had tremendous impact on patient outcomes in breast cancer and are rapidly moving towards second line use. However, many patients fail to respond or relapse after treatment with ADC therapies due to tumor heterogeneity and resistance to ADC payloads. Method: CatenaBio has developed a novel Multi-Payload-Conjugate (MPC) system capable of attaching distinct payloads at different sites to the same antibody, enabling the production of single-molecule targeted combination therapies with defined DAR. Results: We screened combinations of different payloads targeting several different mechanisms attached to trastuzumab at different drug-antibody ratios to optimize tumor cell killing. These targeted combination ADCs demonstrated robust killing in both HER2 high and low tumor cell lines. Conclusion: Antibody Drug Conjugates have revolutionized the treatment of high HER2 positive breast cancer. More recently advances have been made in the design of ADCs to expand indications to include HER2 low as well as HER2 negative patients. These constructs offer the next step in ADC design and allow for the combination of multiple mechanisms of action in a single MPC that are highly effective across multiple breast cancer cell lines. These molecules offer the potential to circumvent tumor resistance pathways and deliver deeper and more durable responses. Disclosures: Marco Lobba, Devin Trinter, Maxwell Nguyen, Daniel Gutierrez, Samantha Brady, Chanez Symister, Andrew Lau, Richard Kendall, and Saurabh Johri are employed by Catena Biosciences. Matthew Francis is a co-founder and advisor to Catena Biosciences. Citation Format: Marco Lobba, Devin Trinter, Maxwell Nguyen, Daniel Gutierrez, Samantha Brady, Chanez Symister, Andrew Lau, Richard Kendall, Saurabh Johri, Matthew Francis. Next generation antibody drug conjugates: Multi-payload conjugates targeting multiple mechanisms of cell killing abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-10.