Table 1.

Summary of study designs and pharmacokinetic (PK) sampling schedules for four single-agent studies of trastuzumab emtansine

Study	No. of enrolled patients	Prior therapies required for eligibility	T-DM1 doses and regimens	PK sampling
TDM3569g, phase I	q3w: n = 24	Trastuzumab	q3w: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg	Intensive sampling in cycle 1; peak/trough PK sampling in subsequent cycles; NCA of PK data
TDM4258g, phase II	112	≥1 HER2-directed therapy and ≥ 1 chemotherapy for MBC	3.6 mg/kg q3w	Frequent sampling in cycles 1 and 4 for NCA of PK data; peak/trough PK sampling in subsequent cycles
TDM4374g, phase II	110	Trastuzumab, lapatinib, capecitabine, a taxane, an anthracycline; ≥ 2 HER2-directed therapies for MBC	3.6 mg/kg q3w	Frequent sampling in cycles 1 and 4 for NCA of PK; peak/trough PK sampling in subsequent cycles
TDM4688g, phase II	51	Trastuzumab	T-DM1 at up to 3.6 mg/kg q3w for 1 yeara	Frequent sampling in cycles 1 and 3 for NCA of PK data; QTc assessment pre- and post-T-DM1 dosing

In all studies, the analytes measured were T-DM1, total trastuzumab, and DM1; incidence of anti-therapeutic antibodies to T-DM1 was also examined

A population PK analysis was conducted using T-DM1 PK data for all studies except TDM4688g

HER2 human epidermal growth factor receptor 2; MBC metastatic breast cancer; NCA noncompartmental analysis; PK pharmacokinetic; q3w every 3 weeks; QTc corrected QT; T-DM1 trastuzumab emtansine

^aThe earliest a patient could begin treatment with T-DM1 in combination with pertuzumab was cycle 4, day 1, after all PK samples for single-agent T-DM1 had been obtained in cycle 3. Pertuzumab dose: 840-mg loading dose, followed by 420 mg q3w for 1 year