Abstract 7180: Tumor growth modeling to support dose justification of Dato-DXd in hormone receptor positive, HER2 negative breast cancer (HR+HER2-BC) subjects

Abstract BACKGROUND: Dato-DXd, a TROP2-directed antibody-drug conjugate, has demonstrated efficacy and a manageable safety profile in multiple tumor types. A dosing regimen of 6 mg/kg every three weeks (Q3W) has been proposed as the optimal schedule based on phase I data in patients with non-small cell lung cancer (NSCLC)1. Dato-DXd demonstrated statistically significant and clinically meaningful improvement in PFS compared with ICC in patients with HR+HER2-BC in TROPION-Breast012. A tumor growth inhibition (TGI) model was developed to support dose justification at 6 mg/kg in HR+HER2-BC subjects. METHODS: A tumor growth inhibition (TGI) model was developed based on tumor size data from HR+HER2-BC patients received 6 mg/kg Dato-DXd Q3W in a Phase I study (N = 39, Data cutoff July 2022). The TGI model described the tumor size as the result of an exponential tumor growth, a tumor shrinkage that was driven by Dato-DXd cycle-specific AUC, and a resistance term suggesting that the shrinkage effect by Dato-DXd decreases over time. Cycle-specific Dato-DXd AUC was derived based on the AUC and time at each cycle for each individual. Simulations were conducted using the TGI model to compare tumor size change from baseline at 4, 6, and 8 mg/kg in HR+HER2-BC patients, with consideration of dropouts. RESULTS: The TGI model well-described tumor size data with reasonable parameter estimations. Simulated time-courses of tumor sizes at Dato-DXd 4, 6, and 8 mg/kg suggested that Dato-DXd at 6 mg/kg may lead to greater tumor shrinkage effect than that at 4 mg/kg in HR+/HER2-BC patients. At approximately 180 days post first treatment, tumor shrinkage at 6 mg/kg was almost 2-times greater than at 4 mg/kg (-51% vs. -25%, respectively). CONCLUSION: Simulations based on the TGI model suggested greater tumor size reduction at Dato-DXd 6 mg/kg compared to 4 mg/kg in HR+HER2-BC patient population. Reference: 1 ACoP13 2022 2 ESMO 2023. Citation Format: Zoey Tang, Yu Jiang, Haitao Yang, David Dai, Chang Gong, Linda Irons, Yuzhuo Pan, Ying Hong, Shuang Liang, Song Ren, Alex Phipps, Diansong Zhou. Tumor growth modeling to support dose justification of Dato-DXd in hormone receptor positive, HER2 negative breast cancer (HR+HER2-BC) subjects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7180.