PII-082 - POPULATION PHARMACOKINETICS (POPPK) OF SACITUZUMAB GOVITECAN (SG) IN PATIENTS (PTS) WITH LOCALLY ADVANCED OR METASTATIC BREAST CANCER (MBC) OR OTHER SOLID TUMORS.

A. Sathe¹, I. Singh¹, A. Jones¹, P. Diderichsen², X. Wang², P. Chang², S. Phan¹, S. Girish¹, A. Othman¹; ¹Gilead Sciences, Foster City, CA, USA, ²Certara, Princeton, NJ, USA.

Background: SG is a novel antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a proprietary, hydrolyzable linker. SG is approved for pts with mTNBC who received ≥2 prior chemotherapies (≥1 in the metastatic setting) and has accelerated approval for pts with metastatic urothelial cancer who received prior platinum-containing chemotherapy and a PD-1/PD-L1 inhibitor. These analyses updated the PK models of SG, Free SN-38, and Total Antibody (tAB) following SG administration using newly available Phase 3 data from pts with HR+/HER2- mBC.

Methods: PopPK models were previously developed to characterize the PK of SG, Free SN-38, and tAB using data from 529 patients in multiple solid tumors [1]. Subsequently, these models were externally validated, and PK parameters were re-estimated with the addition of PK data from 260 pts with HR+/HER2- mBC from Study IMMU-132 09.

Results: Previously developed PopPK models adequately described the data from Study IMMU-132-09. After re-estimation, the typical parameter values for SG clearance and steady-state volume of distribution were 0.128 L/hr and 3.58 L, respectively. Bodyweight-based allometric scaling was included on clearance and volume parameters of all 3 analytes, but with limited impact on the exposure. Overall, mild to moderate renal impairment, mild hepatic impairment, age, sex, baseline albumin level, race, ECOG status, tumor type, UGT1A1 genotype or Trop-2 expression did not have a clinically relevant impact on exposure of the evaluated analytes.

Conclusion: The PK of SG, Free SN-38, and Total Antibody were well characterized using a robust dataset across multiple large trials. The analyses support the approved 10 mg/kg clinical regimen and did not identify a need for dose-adjustment based on any of the evaluated patient demographics or disease characteristics.

1. Sathe AG, Singh I, Singh P, Diderichsen PM, Wang X, Chang P, Phan SC, Girish S and Othman AA: Pharmacokinetics of sacituzumab govitecan in patients with metastatic triple-negative breast cancer and other solid tumors, Annals of Oncology (Abstract#189P), 33, S214, May 2022