Sacituzumab Govitecan Population Pharmacokinetics: Updated Analyses Using HR+/HER2− Metastatic Breast Cancer Data From the Phase 3 TROPiCS-02 Trial

Abstract

Sacituzumab govitecan (SG) is an antibody–drug conjugate composed of a Trop-2–directed antibody coupled to SN-38. SG is approved in multiple countries for pretreated metastatic triple-negative breast cancer (mTNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) mBC. Three previously developed population pharmacokinetic (PopPK) models for SG, free SN-38, and total antibody (tAB) in patients with mTNBC or other solid tumors were externally validated using data from 260 patients with HR+/HER2− mBC from TROPiCS-02 (NCT03901339). Pharmacokinetic parameters were re-estimated using data from 789 patients with HR+/HER2− mBC, mTNBC, or other solid tumors from three studies—TROPiCS-02, ASCENT (NCT02574455), and IMMU-132-01 (NCT01631552). Previously developed PopPK models adequately described the data from TROPiCS-02. Typical parameter estimates based on combined dataset for clearance and steady-state volume of distribution were 0.128 L/h and 3.58 L for SG and 0.0155 L/h and 4.29 L for tAB, respectively. The pharmacokinetics of the three analytes (SG, free SN-38, and tAB) in participants with HR+/HER2− mBC were consistent with those observed in mTNBC and other tumor types. The analyses confirmed mild-to-moderate renal impairment, mild hepatic impairment, age, tumor type (based on limited data in non-breast cancer tumor types), baseline albumin level, UGT1A1 genotype, or Trop-2 expression did not have a clinically relevant impact on the exposure of the three analytes across populations. These findings support that the SG dosing regimen of 10 mg/kg on Days 1 and 8 of 21-day cycles is adequate for patients with HR+/HER2− mBC.