Abstract PO1-04-06: Exposure-response analyses of sacituzumab govitecan efficacy and safety in patients with metastatic breast cancer

Abstract Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate that is composed of an anti Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolysable CL2A linker. SG (10 mg/kg on D1 and D8 of every 21D cycle) is approved for patients (pts) with metastatic triple-negative breast cancer (mTNBC) who received ≥2 prior systemic therapies (≥1 in the metastatic setting). The relationship between exposure of SG, free SN-38, and total antibody (tAB) following SG administration and its efficacy and safety were evaluated in pts with HR+/HER2‒ metastatic breast cancer (mBC) and all pts with mBC (mTNBC or HR+/HER2‒ mBC), respectively. Methods: Available exposure and efficacy outcomes from HR+/HER2‒ mBC pts from phase 3 study TROPiCS-02 (n=260) and safety outcomes from mBC pts in phase 1/2 study IMMU-132-01, phase 3 study ASCENT and TROPiCS-02 (total n=569) were analyzed. Exposure-response (ER) models were developed to characterize the relationship between exposure and efficacy (complete response [CR], overall response rate [ORR], clinical benefit rate [CBR], overall survival [OS] and progression-free survival [PFS]) and safety (adverse events [AEs] of vomiting, diarrhea, hypersensitivity reactions, nausea, neutropenia, febrile neutropenia, time to first dose reduction and first dose delay) endpoints. Exposure metrics of SG, free SN-38, and tAB were evaluated as predictors and effect of clinically relevant covariates was characterized within the modeling framework. Results: Average SG-related serum exposures over the duration of treatment (until the event) were associated with significantly increased efficacy (probability of CR, ORR, CBR and longer OS and PFS) and safety events (probability of any grade AE). Neutropenia was the only AE where the increase in exposure was significantly associated with the increased probability of Grade ≥3 and Grade 4 events. Baseline Trop-2 expression level was not correlated with assessed efficacy and safety endpoints. Conclusions: Within the exposure range achieved with the 10 mg/kg regimen, higher exposure values were associated with a higher probability of achieving better efficacy. The 10 mg/kg SG dose achieved an acceptable balance between efficacy and safety which supports the appropriateness of this regimen in pts with HR+/HER2‒ mBC. Citation Format: Indrajeet Singh, Abhishek Sathe, Paul Diderichsen, Han Witjes, Arne Van Schanke, John Maringwa, Wendy Verret, Sandhya Girish, Ahmed Othman. Exposure-response analyses of sacituzumab govitecan efficacy and safety in patients with metastatic breast cancer [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 PO1-04-06.