This is an open-label Phase I study of single-agent trastuzumab emtansine administered by intravenous (IV) infusion. The study will characterize the pharmacokinetics of trastuzumab emtansine and its relevant analytes and the safety of trastuzumab emtansine in Chinese participants with human epidermal growth factor receptor 2 (HER2)-positive locally advanced/metastatic breast cancer (LA/MBC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Trastuzumab emtansine will be administered by IV infusion at a dose of 3.6 milligrams per kilogram (mg/kg) of body weight, every three weeks (Q3W) until death, disease progression or unmanageable toxicity.
Fudan University Shanghai Cancer Center; Medical Oncology
Shanghai, China
Area Under the Concentration-Time Curve [AUC] of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
AUC will be evaluated and reported for trastuzumab emtansine and its metabolites.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Maximum Serum Concentration (Cmax) Immediately After Dosing of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
Maximum serum concentration (Cmax) immediately after dosing will be evaluated and reported for trastuzumab emtansine and its metabolites.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Minimum (Trough) Concentration (Cmin) of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
Minimum (Trough) Concentration (Cmin) will be evaluated and reported for trastuzumab emtansine and its metabolites.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Clearance (CL) of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
Clearance (CL) will be evaluated and reported for trastuzumab emtansine and its metabolites.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Volume of Distribution at Steady-State (Vss) of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
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Volume of distribution at steady-state (Vss) will be evaluated and reported.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Half-Life (t1/2) of Trastuzumab Emtansine, Total Trastuzumab, N2'-Deacetyl-N2'-(3-Mercapto-1-Oxopropyl)-Maytansine (DM1), Non-reducible Thioether Linkage (MCC)-DM1 and Lys-MCC-DM1
Half-life (t1/2) will be evaluated and reported.
Time frame: Pre-dose, 30 minutes (min), 24, 48, 72/96 hours (hr) post-dose, Day 8, 11, 15, 18 post-dose; Pre-dose, 30 min post-dose Cycle 2 Day 1, Cycle 3 Day 1; Pre-dose Cycle 4 Day 1
Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for AEs, Version 4.03 (NCI CTCAE V4.03)
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug.
Time frame: Up to (28-42 days) after the last dose of study drug (57 days)