ADC ID	DRG0CYMEB
ADC Name	Trastuzumab emtansine
Brand Name	Kadcyla
Synonyms	trastuzumab emtansine; ado-trastuzumab emtansine; Kadcyla; RG3502; RO5304020; T-DM1; trastuzumab-DM1; trastuzumab-MCC-DM1; trastuzumab-emtansine; RG3502-10    Click to Show/Hide
Organization	ImmunoGen (Top20 MNC) (Originator);Genentech (Top20 MNC)
Drug Status	Approved in 2013
Drug-to-Antibody Ratio	3.5
Structure
				2D MOL
Antibody Name	Trastuzumab					Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)					Antigen Info
Payload Name	DM1					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)					Linker Info
Conjugate Type	Random Lysines
Combination Type	emtansine
Absorption	The absorption/ bioavailability should be close to 100% since trastuzumab emtansine is administered IV
Distribution	The volume of distribution of trastuzumab emtansine is about 3.13 L. DM1 has a plasma protein binding value of 93%
Metabolism	Trastuzumab emtansine undergoes lysosomal degradation to MCC-DM1, Lys-MCC-DM1, and DM1. All of these products are detected at low levels in the plasma. DM1 undergoes further degradation by CYP3A4 and CYP3A5, but DM1 does not induce or inhibit any of the CYP450 enzymes. Trastuzumab emtansine has a long half life of about 4 days.
Toxicity	The FDA label includes a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity.
Special Approval(s)	Breakthrough therapy (FDA); Fast track (FDA); Priority review (NMPA)

Bystander Killing Effect	Description	Reference
no	Undisclosed	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	83.4	ug/mL	The maximum concentrations (Cmax) of trastuzumab emtansine was observed close to the end of infusion, with mean values of 83.4 ug/ mL.	[1]
Area Under the Concentration-Time Curve (AUC)	14.5	day*ug/mL	After every-3-week (q3w) dosing, the AUC (0.3mg/kg, n=3) of T-DM1 is 14.5 day·ug/mL.	[1]
Maximum Observed Concentration (Cmax)	35.3	ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1	[5]
Maximum Observed Concentration (Cmax)	43.4	ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4	[5]
Maximum Observed Concentration (Cmax)	82	ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5	[5]
Area Under the Concentration-Time Curve (AUC)	139	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1,area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	203	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	338	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	141	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	204	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	346	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	367.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age<65	[3]
Maximum Observed Concentration (Cmax)	80.67	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age<65	[3]
Area Under the Concentration-Time Curve (AUC)	367	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age 65-75 years	[3]
Maximum Observed Concentration (Cmax)	81.47	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age 65-75 years	[3]
Area Under the Concentration-Time Curve (AUC)	370.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age >75 years	[3]
Maximum Observed Concentration (Cmax)	80.36	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age >75 years	[3]
Area Under the Concentration-Time Curve (AUC)	369.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Non-Asian	[3]
Maximum Observed Concentration (Cmax)	81.03	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Non-Asian	[3]
Area Under the Concentration-Time Curve (AUC)	346.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asian	[3]
Maximum Observed Concentration (Cmax)	78.53	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asian	[3]
Area Under the Concentration-Time Curve (AUC)	365.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, US	[3]
Maximum Observed Concentration (Cmax)	79.81	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, US	[3]
Area Under the Concentration-Time Curve (AUC)	375.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Western Europe	[3]
Maximum Observed Concentration (Cmax)	83.79	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Western Europe	[3]
Area Under the Concentration-Time Curve (AUC)	351	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asia	[3]
Maximum Observed Concentration (Cmax)	78.11	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asia	[3]
Area Under the Concentration-Time Curve (AUC)	372.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Other	[3]
Maximum Observed Concentration (Cmax)	82.15	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Other	[3]
Area Under the Concentration-Time Curve (AUC)	391.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Normal Renal function	[3]
Maximum Observed Concentration (Cmax)	85.45	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Normal Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	360.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, mild impairment Renal function	[3]
Maximum Observed Concentration (Cmax)	79.6	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, mild impairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	350.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Moderate mpairment Renal function	[3]
Maximum Observed Concentration (Cmax)	77.65	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Moderate mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	375.5	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Severe mpairment Renal function	[3]
Maximum Observed Concentration (Cmax)	78.08	ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Severe mpairment Renal function	[3]
Maximum Observed Concentration (Cmax)	80.9±15.5	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Maximum Observed Concentration (Cmax)	75.6±16.3	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Maximum Observed Concentration (Cmax)	60.9±12.8	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	377±88.5	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	232±96.1	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	126±67.9	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Maximum Observed Concentration (Cmax)	77.9±27	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Maximum Observed Concentration (Cmax)	71±25.5	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Maximum Observed Concentration (Cmax)	66.5±4.3	ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	488±146	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	418±164	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	328	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	14.5	day*ug/mL	After every-3-week (q3w) dosing, the AUC (0.3mg/kg, n=3) of T-DM1 is 14.5 day·ug/mL.	[1]
Volume of Distribution (Vd)	3.13	L	The central volume of distribution of trastuzumab emtansine was 3.13 L	[1]
Volume of Distribution (Vd)	3.21	L	Final model estimates for the volume of distribution of T-DM1 (VTDM) were relatively low, similar to average adult plasma volume.	[2]
Volume of Distribution (Vd)	11	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Central volume    Click to Show/Hide	[4]
Volume of Distribution (Vd)	3.44	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Peripheral volume 2    Click to Show/Hide	[4]
Volume of Distribution (Vd)	148	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Central volume    Click to Show/Hide	[4]
Volume of Distribution (Vd)	57.2	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Peripheral volume 2    Click to Show/Hide	[4]
Volume of Distribution (Vd)	10.7	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Central volume    Click to Show/Hide	[4]
Volume of Distribution (Vd)	2.52	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Peripheral volume 2    Click to Show/Hide	[4]
Volume of Distribution (Vd)	154	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Central volume    Click to Show/Hide	[4]
Volume of Distribution (Vd)	50	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Peripheral volume 2    Click to Show/Hide	[4]
Area Under the Concentration-Time Curve (AUC)	139	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1,area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	203	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	338	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	141	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	204	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	346	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Volume of Distribution (Vd)	57.1	mL/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, volume of distribution, steady state	[5]
Volume of Distribution (Vd)	67.6	mL/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, volume of distribution, steady state	[5]
Volume of Distribution (Vd)	59.1	mL/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, volume of distribution, steady state	[5]
Area Under the Concentration-Time Curve (AUC)	367.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age<65	[3]
Area Under the Concentration-Time Curve (AUC)	367	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age 65-75 years	[3]
Area Under the Concentration-Time Curve (AUC)	370.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age >75 years	[3]
Area Under the Concentration-Time Curve (AUC)	369.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Non-Asian	[3]
Area Under the Concentration-Time Curve (AUC)	346.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asian	[3]
Area Under the Concentration-Time Curve (AUC)	365.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, US	[3]
Area Under the Concentration-Time Curve (AUC)	375.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Western Europe	[3]
Area Under the Concentration-Time Curve (AUC)	351	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asia	[3]
Area Under the Concentration-Time Curve (AUC)	372.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Other	[3]
Area Under the Concentration-Time Curve (AUC)	391.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Normal Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	360.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, mild impairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	350.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Moderate mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	375.5	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Severe mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	377±88.5	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	232±96.1	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	126±67.9	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	52.1±9.61	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	53.5±10.7	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	78.4±42.9	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	488±146	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	418±164	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	328	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	40.5±30.1	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	36.2±31.3	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	20.4	mL/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	3.37	L	An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer, Central volume of distribution    Click to Show/Hide	[7]
Volume of Distribution (Vd)	0.974	L	An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer, T-DM1 peripheral volume of distribution    Click to Show/Hide	[7]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	14.5	day*ug/mL	After every-3-week (q3w) dosing, the AUC (0.3mg/kg, n=3) of T-DM1 is 14.5 day·ug/mL.	[1]
Area Under the Concentration-Time Curve (AUC)	139	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1,area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	203	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	338	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	141	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	204	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	346	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	367.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age<65	[3]
Area Under the Concentration-Time Curve (AUC)	367	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age 65-75 years	[3]
Area Under the Concentration-Time Curve (AUC)	370.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age >75 years	[3]
Area Under the Concentration-Time Curve (AUC)	369.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Non-Asian	[3]
Area Under the Concentration-Time Curve (AUC)	346.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asian	[3]
Area Under the Concentration-Time Curve (AUC)	365.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, US	[3]
Area Under the Concentration-Time Curve (AUC)	375.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Western Europe	[3]
Area Under the Concentration-Time Curve (AUC)	351	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asia	[3]
Area Under the Concentration-Time Curve (AUC)	372.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Other	[3]
Area Under the Concentration-Time Curve (AUC)	391.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Normal Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	360.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, mild impairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	350.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Moderate mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	375.5	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Severe mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	377±88.5	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	232±96.1	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	126±67.9	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	488±146	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	418±164	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	328	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	4	days	Trastuzumab emtansine has a long half life of about 4 days.	[1]
Clearance (CL)	0.68	L/day	After IV infusion, trastuzumab emtansine has a clearance of 0.68 L/day.	[1]
Area Under the Concentration-Time Curve (AUC)	14.5	day*ug/mL	After every-3-week (q3w) dosing, the AUC (0.3mg/kg, n=3) of T-DM1 is 14.5 day·ug/mL.	[1]
Clearance (CL)	0.0618	L/h	Noncompartmental analysis showed concentration-dependent clearance for T-DM1 (0.3 mg/kg). Administered to phase I patients in once-every-3-weeks and once-weekly regimens.	[2]
Clearance (CL)	0.0232	L/h	Noncompartmental analysis showed concentration-dependent clearance for T-DM1 (4.8 mg/kg). Administered to phase I patients in once-every-3-weeks and once-weekly regimens.	[2]
Elimination Half-Life (t1/2)	4	days	Terminal half-life in phase II and III studies (3.6 mg/kg q3w).	[3]
Clearance (CL)	2.42	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Total trastuzumab clearance    Click to Show/Hide	[4]
Clearance (CL)	49	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Distributional clearance 2    Click to Show/Hide	[4]
Clearance (CL)	12	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Distributional clearance 3    Click to Show/Hide	[4]
Elimination Half-Life (t1/2)	16.7	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Rat Peripheral volume 3    Click to Show/Hide	[4]
Clearance (CL)	17.4	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Total trastuzumab clearance    Click to Show/Hide	[4]
Clearance (CL)	25.5	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Distributional clearance 2    Click to Show/Hide	[4]
Clearance (CL)	81.2	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Distributional clearance 3    Click to Show/Hide	[4]
Elimination Half-Life (t1/2)	127	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Mechanistic T-DM1 PK Model Parameter Estimates, Cynomolgus monkey Peripheral volume 3    Click to Show/Hide	[4]
Clearance (CL)	2.37	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Total trastuzumab clearance    Click to Show/Hide	[4]
Clearance (CL)	59.7	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Distributional clearance 2    Click to Show/Hide	[4]
Clearance (CL)	13.9	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Distributional clearance 3    Click to Show/Hide	[4]
Elimination Half-Life (t1/2)	15.5	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Rat Peripheral volume 3    Click to Show/Hide	[4]
Clearance (CL)	19.9	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Total trastuzumab clearance    Click to Show/Hide	[4]
Clearance (CL)	56.8	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Distributional clearance 2    Click to Show/Hide	[4]
Clearance (CL)	60.4	mL/day	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Distributional clearance 3    Click to Show/Hide	[4]
Elimination Half-Life (t1/2)	84.7	mL	A Mechanistic Pharmacokinetic Model Elucidating the Disposition of Trastuzumab Emtansine (T-DM1), an Antibody-Drug Conjugate (ADC) for Treatment of Metastatic Breast Cancer, Reduced T-DM1 PK Model Parameter Estimates Estimates, Cynomolgus monkey Peripheral volume 3    Click to Show/Hide	[4]
Area Under the Concentration-Time Curve (AUC)	139	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1,area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	203	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	338	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero to the last measurable concentration	[5]
Area Under the Concentration-Time Curve (AUC)	141	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	204	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Area Under the Concentration-Time Curve (AUC)	346	day*ug/mL	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, area under the serum concentration-time curve from time zero extrapolated to infinity	[5]
Elimination Half-Life (t1/2)	2.39	day	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1	[5]
Elimination Half-Life (t1/2)	2.88	day	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4	[5]
Elimination Half-Life (t1/2)	3.74	day	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5	[5]
Clearance (CL)	12.9	mL/day/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 1.8mg/kg (Dose), N=1, volume of distribution, steady state	[5]
Clearance (CL)	13.4	mL/day/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 2.4 mg/kg (Dose), N=4, volume of distribution, steady state	[5]
Clearance (CL)	10.6	mL/day/kg	Pharmacokinetic parameters of T-DM1, total trastuzumab and DM1 in Cycle 1, 3.6 mg/kg (Dose), N=5, volume of distribution, steady state	[5]
Area Under the Concentration-Time Curve (AUC)	367.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age<65	[3]
Area Under the Concentration-Time Curve (AUC)	367	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age 65-75 years	[3]
Area Under the Concentration-Time Curve (AUC)	370.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Age >75 years	[3]
Area Under the Concentration-Time Curve (AUC)	369.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Non-Asian	[3]
Area Under the Concentration-Time Curve (AUC)	346.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asian	[3]
Area Under the Concentration-Time Curve (AUC)	365.8	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, US	[3]
Area Under the Concentration-Time Curve (AUC)	375.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Western Europe	[3]
Area Under the Concentration-Time Curve (AUC)	351	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Asia	[3]
Area Under the Concentration-Time Curve (AUC)	372.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Other	[3]
Area Under the Concentration-Time Curve (AUC)	391.6	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Normal Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	360.1	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, mild impairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	350.2	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Moderate mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	375.5	day*ug/mL	On steady-state T-DM1 exposure after repeated dosing of 3.6 mg/kg by 0.5-h IV infusion q3w, Severe mpairment Renal function	[3]
Area Under the Concentration-Time Curve (AUC)	377±88.5	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	232±96.1	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	126±67.9	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	3.32±0.678	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	2.23±0.782	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	2.57±1.65	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Clearance (CL)	9.94±2.1	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Clearance (CL)	18.2±7.93	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Clearance (CL)	39.7±26.2	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 1.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	488±146	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	418±164	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	328	day*ug/mL	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	3.82±0.698	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	3.23±0.856	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	2.67	day	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Clearance (CL)	8.16±3.27	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Clearance (CL)	9.74±3.62	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Mild Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Clearance (CL)	8.99	mL/day/kg	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Moderate Hepatic Function, Mean pharmacokinetic parameters for T-DM1 at cycles 3.    Click to Show/Hide	[6]
Clearance (CL)	0.403	L/day	An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer, T-DM1 deconjugation clearance    Click to Show/Hide	[7]
Clearance (CL)	0.305	L/day	An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer, T-DM1 proteolytic degradation clearance    Click to Show/Hide	[7]
Clearance (CL)	0.737	L/day	An Integrated Multiple-Analyte Pharmacokinetic Model to Characterize Trastuzumab Emtansine (T-DM1) Clearance Pathways and to Evaluate Reduced Pharmacokinetic Sampling in Patients with HER2-Positive Metastatic Breast Cancer, T-DM1 distributional clearance    Click to Show/Hide	[7]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT01702571	Phase 3	A two-cohort, open-label, multicenter study of trastuzumab emtansine (T-DM1) in HER2-positive locally advanced or metastatic breast cancer patients who have received prior anti-HER2 and chemotherapy-based treatment.    Click to Show/Hide
Objective Response Rate (ORR)	NCT02999672	Phase 2	A study to determine best tumor response with trastuzumab emtansine in human epidermal growth factor receptor 2 (HER2) overexpressing solid tumors (KAMELEON).
Objective Response Rate (ORR)	NCT02465060	Phase 2	Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas, or multiple myeloma (the MATCH screening trial).
Objective Response Rate (ORR)	NCT02924883	Phase 2	A randomized, multicenter, double-blind, placebo-controlled phase II study of the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab and taxane based therapy.    Click to Show/Hide
Objective Response Rate (ORR)	NCT03032107	Phase 1b	A phase 1b study of pembrolizumab in combination with trastuzumab-dm1 in metastatic HER2-positive breast cancer.
Undisclosed	NCT01966471	Phase 3	A randomized, multicenter, open-label, phase 3 trial comparing trastuzumab plus pertuzumab plus a taxane following anthracyclines versus trastuzumab emtansine plus pertuzumab following anthracyclines as adjuvant therapy in patients with operable HER2-positive primary breast cancer.    Click to Show/Hide

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 1.1	%	Breast cancer PDX model (PDX: ST565)
Tumor Growth Inhibition value (TGI)	≈ 19.2	%	Breast cancer PDX model (PDX: ST313)
Tumor Growth Inhibition value (TGI)	≈ 37.6	%	Gastric cancer PDX model (PDX model: NIBIO G016)
Tumor Growth Inhibition value (TGI)	≈ 85.2	%	Breast cancer PDX model (PDX: ST225)
Tumor Growth Inhibition value (TGI)	≈ 90.4	%	Breast cancer PDX model (PDX: PDX12)

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 7.1	%	CFPAC-1 cells	Pancreatic ductal adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 15.5	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 27.1	%	BT-474 EEI cells	Invasive breast carcinoma of no special type
Tumor Growth Inhibition value (TGI)	≈ 31.7	%	Capan-1 cells	Pancreatic ductal adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 33.1	%	GCIY cells	Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 36	%	SW48 cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 36	%	SW48 cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 42	%	11-18 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 42	%	11-18 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 43.3	%	BT-474 cells (Trastuzumab emtansine resistant)	Invasive breast carcinoma
Tumor Growth Inhibition value (TGI)	≈ 45	%	SK-OV-3 cells (YES1 Y537F expression)	Ovarian serous cystadenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 45.5	%	BT-474 EEI cells	Invasive breast carcinoma of no special type
Tumor Growth Inhibition value (TGI)	≈ 46.2	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 55	%	HT-29 cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 55	%	HT-29 cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 58.5	%	JIMT-1 cells	Breast ductal carcinoma
Tumor Growth Inhibition value (TGI)	≈ 58.7	%	BT-474 EEI cells	Invasive breast carcinoma of no special type
Tumor Growth Inhibition value (TGI)	≈ 63	%	NCI-H3255 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 63	%	NCI-H3255 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 63.3	%	LS174T cells	Colon adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 66.7	%	HCC827 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 74	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 76.54	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 82.9	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 83.9	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 84.39	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 88.7	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 90.1	%	MMTV-HER2 cells	Breast cancer
Tumor Growth Inhibition value (TGI)	≈ 90.7	%	BT-474 EEI cells	Invasive breast carcinoma of no special type
Tumor Growth Inhibition value (TGI)	≈ 92.3	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 98.7	%	BT-474 EEI cells	Invasive breast carcinoma of no special type
Tumor Growth Inhibition value (TGI)	≈ 99.4	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 100	%	KMCH-1 cells	Combined hepatocellular carcinoma and cholangiocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 100	%	HCC1954 cells	Breast ductal carcinoma
Minimal Effective Dose (MED)	< 5	mg/kg	NCI-N87 cells	Gastric tubular adenocarcinoma
Maximum Tolerated Dose (MTD)	> 20	mg/kg	NCI-N87 cells	Gastric tubular adenocarcinoma

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 94.98	%	Breast cancer model MMTV-HER2 Fo5

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.04	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.14	nM	SK-OV-3 cells	Ovarian serous cystadenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.24	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.24	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.26	nM	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.57	nM	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.76	nM	JIMT-1 cells	Breast ductal carcinoma
Half Maximal Inhibitory Concentration (IC50)	2.71	nM	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	5.89	nM	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	6.4	nM	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	18.37	nM	MDA-MB-468 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 50	nM	MCF-7 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	> 100	nM	MCF-7 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	220	nM	MDA-MB-468 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	317	nM	HCC827 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 500	nM	MCF-7 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	8.00-15.00	ng/mL	CVCL_0033	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0	ug/mL	BT-474 EEI cells	Invasive breast carcinoma of no special type
Half Maximal Inhibitory Concentration (IC50)	0.01	ug/mL	SK-OV-3 cells	Ovarian serous cystadenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.01	ug/mL	KPL-4 cells	Breast inflammatory carcinoma
Half Maximal Inhibitory Concentration (IC50)	0.03	ug/mL	HCC1954 cells	Breast ductal carcinoma
Half Maximal Inhibitory Concentration (IC50)	0.06	ug/mL	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	0.27	ug/mL	MKN7 cells	Gastric tubular adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Objective Response Rate (ORR)	21.40%	Positive HER2 expression (HER2 +++/++)
Patients Enrolled	Untreated, asymptomatic BM or controlled brain disease treated with radiotherapy >14 days before enrollment; had received prior HER2-targeted therapy and chemotherapy; and had progressed on or after their most recent treatment of advanced breast cancer.
Administration Dosage	3.6 mg/kg intravenously every 3 weeks.
Related Clinical Trial
NCT Number	NCT01702571	Clinical Status	Phase 3
Clinical Description	A two-cohort, open-label, multicenter study of trastuzumab emtansine (T-DM1) in HER2-positive locally advanced or metastatic breast cancer patients who have received prior anti-HER2 and chemotherapy-based treatment.
Primary Endpoint	Objective response rate=21.40% (95% CI 14.60-29.60), clinical benefit rate=42.90% (95% CI 34.10-52.00).
Other Endpoint	Median PFS=5.50 months (95% CI, 5.30-5.60), overall survival =18.90 months (95% CI, 17.10-21.30).
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Objective Response Rate (ORR)	5.10%	Positive HER2 expression (HER2+++/++)
Patients Enrolled	HER2 positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma
Administration Dosage	Received singleagent TDM1 2.4 mg/kg once weekly (qw) or 3.6 mg/kg every 3 weeks (q3w).
Related Clinical Trial
NCT Number	NCT02999672	Clinical Status	Phase 2
Clinical Description	A study to determine best tumor response with trastuzumab emtansine in human epidermal growth factor receptor 2 (HER2) overexpressing solid tumors (KAMELEON).
Primary Endpoint	BOR, Urothelial bladder cancer (n=13); PR N=5 (38.46%);SD N=1 (7.7%);PD N=6 (46.2%);NE N=1 (7.69%). Pancreatic cancer/cholangiocarcinoma (n=7) PR N=1 (14.29%);SD N=3 (42.86%);PD N=2 (28.57%); NE N=1 (14.29%).
Other Endpoint	PFS, Urothelial bladder cancer (n=13), Median PFS, months (95% CI) 2.20 (1.18-4.30), Median OS, months (95% CI) 7.03 (3.75-NE). Pancreatic cancer/cholangiocarcinoma (n=7), Median PFS, months (95% CI) 2.58 (1.31-9.99), Median OS, months (95% CI) NE (1.45-NE).
Experiment 3 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Objective Response Rate (ORR)	5.60%
Patients Enrolled	38 patients were enrolled and 36 included in efficacy analysis.Patients were treated with the standard intravenous dosing of T- DM1, that is 3.6mg/kg every 3 weeks for a 21-day cycle.
Administration Dosage	3.6 mg/kg every 3 weeks for a 21-day cycle, until toxicity or progression.
Related Clinical Trial
NCT Number	NCT02465060	Clinical Status	Phase 2
Clinical Description	Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas, or multiple myeloma (the MATCH screening trial).
Primary Endpoint	ORR was 2/36 (5.56%) with 90% confidence interval (90% CI, 1.00% to 16.50%)
Other Endpoint	PFS=23.60%.
Experiment 4 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Objective Response Rate (ORR)	45%	Positive HER2 expression (HER2 +++/++)
Patients Enrolled	An Eastern Cooperative Oncology Group performance status of 0 or 1 and centrally confirmed, measurable, HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.
Administration Dosage	3.6 mg/kg ( trastuzumab emtansine) and 1200 mg (Atezolizumab) intravenously every 3 weeks.
Related Clinical Trial
NCT Number	NCT02924883	Clinical Status	Phase 2
Clinical Description	A randomized, multicenter, double-blind, placebo-controlled phase II study of the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab and taxane based therapy.
Primary Endpoint	Median PFS=8.20 months (95% CI 5.80-10.70).
Other Endpoint	Median overall survival was not estimable (95% CI NE-NE); Objective response rate=45.00% (95% CI 28.06-50.30).
Experiment 5 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Objective Response Rate (ORR)	20%	High HER2 expression (HER2+++)
Patients Enrolled	HER2-positive, metastatic breast cancer previously treated with taxane, trastuzumab, and pertuzumab, and were T-DM1-nave.
Administration Dosage	The study consisted of a dose de-escalation (dose-finding) cohort, followed by an expansion cohort at the recommended phase II dose (RP2D), T-DM1 3.60 mg/kg intravenously every 21 days, and pembrolizumab 200mg intravenously every 21 days, if one or fewer DLTs were noted in the first six patients at that dose level, it would be declared the RP2D.
Related Clinical Trial
NCT Number	NCT03032107	Clinical Status	Phase 1b
Clinical Description	A phase 1b study of pembrolizumab in combination with trastuzumab-dm1 in metastatic HER2-positive breast cancer.
Primary Endpoint	OrR=20.00% (95% CI 5.70%-43.70%), and median PFS=9.60 months (95%CI 2.80-16.00 months).
Other Endpoint	There were no dose-limiting toxicities. The RP2D was 3.60 mg/kg T-DM1 plus 200 mg pembrolizumab every 21 days.
Experiment 6 Reporting the Activity Date of This ADC					[13]
Patients Enrolled	Newly diagnosed, HER2-positive, nonmetastatic, histologically confirmed, operable primary invasive breast carcinoma.
Administration Dosage	T-DM1 was dosed at 3.60 mg/kg once every 3 weeks. Trastuzumab was dosed at 6 mg/kg once every 3 weeks after an 8 mg/kg loading dose and started concurrently with the taxane. Pertuzumab was dosed at 420 mg once every 3 weeks after an 840 mg loading dose and administered concurrently with T-DM1 or trastuzumab-plus-taxane. An interval of 3 weeks from the last dose of anthracycline to initiation of HER2-targeted therapy was required. After the taxane-concurrent phase in the trastuzumab-containing arm, trastuzumab-plus-pertuzumab was continued for 1 year. In the T-DM1containing arm, T-DM1-plus-pertuzumab was continued for 1 year.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT01966471	Clinical Status	Phase 3
Clinical Description	A randomized, multicenter, open-label, phase 3 trial comparing trastuzumab plus pertuzumab plus a taxane following anthracyclines versus trastuzumab emtansine plus pertuzumab following anthracyclines as adjuvant therapy in patients with operable HER2-positive primary breast cancer.
Primary Endpoint	82 (9.90%) IDFS events had occurred in the AC-THP arm and 80 (9.60%) had occurred in the AC-KP arm.
Other Endpoint	3-year IDFS rates were 94.10% (95% CI, 92.50 to 95.70) with AC-THP and 92.80% (95% CI, 91.00 to 94.50) with AC-KP.

Experiment 1 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 1.10%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of T-DM1 was evaluated in various patient-derived xenograft models with different HER2 expression levels. Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Breast cancer PDX model (PDX: ST565)
Experiment 2 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 19.20%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of T-DM1 was evaluated in various patient-derived xenograft models with different HER2 expression levels. Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Breast cancer PDX model (PDX: ST313)
Experiment 3 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 37.60%	High HER2 expression (HER2+++)
Method Description	The antitumor activity of T-DM1 was evaluated in various patient-derived xenograft models with different HER2 expression levels. Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX model (PDX model: NIBIO G016)
Experiment 4 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 85.20%	Moderate HER2 expression (HER2++)
Method Description	The antitumor activity of T-DM1 was evaluated in various patient-derived xenograft models with different HER2 expression levels. Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Breast cancer PDX model (PDX: ST225)
Experiment 5 Reporting the Activity Date of This ADC					[15]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.40%	Positive HER2 expression (HER2+++/++)
Method Description	T-DM1 (Genentech) was administered i.p. at 10 mg/kg once per week.
In Vivo Model	Breast cancer PDX model (PDX: PDX12)

Experiment 1 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 7.10%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of T-DM1 was evaluated in various mice xenograft models with different HER2 expression levels; CFPAC-1 (low-expression). Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	CFPAC-1 cell line xenograft model
In Vitro Model	Cystic fibrosis	CFPAC-1 cells		CVCL_1119
Experiment 2 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 15.50%	High HER2 expression (HER2+++)
Method Description	The activity of trastuzumab-MCC-DM1 was further investigated in trastuzumab-insensitive mouse xenograft model. After transplantation of MMTV-HER2 Fo5 mammary tumor explants, tumor-bearing nude mice (n = 8 mice per group) were treated once every 3 weeks with 1 mg/kg trastuzmab-MCC-DM1.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 3 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 27.10%	High HER2 expression (HER2+++)
Method Description	Naive female beige nude XID mice were inoculated in the mammary fat pad with 20 million tumor cells suspended in 50% phenol redfree Matrigel mixed with culture medium. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Nude mice with established tumors were dosed i.v. with Tmab-MCC-DM1 0.3 mg/kg for a total of three injections.    Click to Show/Hide
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 4 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 31.70%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of T-DM1 was evaluated in various mice xenograft models with different HER2 expression levels; Capan-1 (weak positive). Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Capan-1 cell line xenograft model
In Vitro Model	Pancreatic ductal adenocarcinoma	Capan-1 cells		CVCL_0237
Experiment 5 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 33.10%	Negative HER2 expression (HER2-)
Method Description	The antitumor activity of T-DM1 was evaluated in various mice xenograft models with different HER2 expression levels; GCIY (negative). Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	GCIY cell line xenograft model
In Vitro Model	Gastric adenocarcinoma	GCIY cells		CVCL_1228
Experiment 6 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 36%	Positive HER2 expression (HER2+++/++)
Method Description	Subcutaneous injection of 100,000 cells mixed in 200 mL PBS solution was performed. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 at a dose of 300 mg/kg via IP injection.
In Vivo Model	SW48 CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 7 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 36%	Low HER2 expression (HER2 +)
Method Description	SW48, HT-29 and LS174T cells were injected into null mice subcutaneously, followed by treatment with cetuximab, trastuzumab and T-DM1. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 at a dose of 300 mg/kg via IP injection.
In Vivo Model	SW48 CDX model
In Vitro Model	Colon adenocarcinoma	SW48 cells		CVCL_1724
Experiment 8 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 42%	Low HER2 expression (HER2+)
Method Description	Subcutaneous injection of 100,000 cells mixed in 200 mL PBS solution was performed. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 (30 mg/kg, once per week i.p.) for 8 weeks.
In Vivo Model	11-18 CDX model
In Vitro Model	Lung adenocarcinoma	11-18 cells		CVCL_6659
Experiment 9 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 42%	Low HER2 expression (HER2 +)
Method Description	11-18 cells (4,000,000 ) and HCC827 cells (2,000,000 ) were injected subcutaneously into the backs on both sides of the mice. T-DM1 (30 mg/kg, once per week i.p.) for 8 weeks.
In Vivo Model	11-18 CDX model
In Vitro Model	Lung adenocarcinoma	11-18 cells		CVCL_6659
Experiment 10 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 43.30%	Positive HER2 expression (HER2 +++/++)
Method Description	Trastuzumab-emtansine (3 mg/kg, every seven days 4) induces efficient tumor cell killing in cell line-derived models of BT-474/R1-7 cells with HER2 expression with high expression.
In Vivo Model	BT-474 CDX model (T-DM1 resistant)
In Vitro Model	Invasive breast carcinoma	BT-474 cells (Trastuzumab emtansine resistant)		CVCL_0179
Experiment 11 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45%	Positive HER2 expression (HER2 +++/++)
Method Description	Trastuzumab-emtansine (3 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of SK-OV-3 cells with HER2 expression with high expression.
In Vivo Model	SK-OV-3 CDX model (Expressing YES1 Y537F)
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells (YES1 Y537F expression)		CVCL_0532
Experiment 12 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.50%	High HER2 expression (HER2+++)
Method Description	Naive female beige nude XID mice were inoculated in the mammary fat pad with 20 million tumor cells suspended in 50% phenol redfree Matrigel mixed with culture medium. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Nude mice with established tumors were dosed i.v. with Tmab-MCC-DM1 1 mg/kg for a total of three injections.    Click to Show/Hide
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 13 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 46.20%	High HER2 expression (HER2+++)
Method Description	The activity of trastuzumab-MCC-DM1 was further investigated in trastuzumab-insensitive mouse xenograft model. After transplantation of MMTV-HER2 Fo5 mammary tumor explants, tumor-bearing nude mice (n = 8 mice per group) were treated once every 3 weeks with 3 mg/kg trastuzmab-MCC-DM1.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 14 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 55%	Positive HER2 expression (HER2+++/++)
Method Description	Subcutaneous injection of 100,000 cells mixed in 200 mL PBS solution was performed. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 at a dose of 300 mg/kg via IP injection.
In Vivo Model	HT-29 CDX model
In Vitro Model	Colon adenocarcinoma	HT-29 cells		CVCL_0320
Experiment 15 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 55%	Moderate HER2 expression (HER2 ++)
Method Description	SW48, HT-29 and LS174T cells were injected into null mice subcutaneously, followed by treatment with cetuximab, trastuzumab and T-DM1. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 at a dose of 300 mg/kg via IP injection.
In Vivo Model	HT-29 CDX model
In Vitro Model	Colon adenocarcinoma	HT-29 cells		CVCL_0320
Experiment 16 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 58.50%	Moderate HER2 expression (HER2++)
Method Description	The antitumor activity of T-DM1 was evaluated in various mice xenograft models with different HER2 expression levels; JIMT-1 (moderate positive). Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	JIMT-1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 17 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 58.70%	High HER2 expression (HER2+++)
Method Description	Naive female beige nude XID mice were inoculated in the mammary fat pad with 20 million tumor cells suspended in 50% phenol redfree Matrigel mixed with culture medium. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Nude mice with established tumors were dosed i.v. with Tmab-MCC-DM1 3 mg/kg for a total of three injections.    Click to Show/Hide
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 18 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 63%	Positive HER2 expression (HER2+++/++)
Method Description	Subcutaneous injection of 100,000 cells mixed in 200 mL PBS solution was performed. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 (30 mg/kg, once per week i.p.) for 8 weeks.
In Vivo Model	H3255 CDX model
In Vitro Model	Lung adenocarcinoma	NCI-H3255 cells		CVCL_6831
Experiment 19 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 63%	High HER2 expression (HER2 +++)
Method Description	T-DM1 (30 mg/kg, once per week i.p.) for 8 weeks,.
In Vivo Model	H3255 CDX model
In Vitro Model	Lung adenocarcinoma	NCI-H3255 cells		CVCL_6831
Experiment 20 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 63.30%	High HER2 expression (HER2 +++)
Method Description	SW48, HT-29 and LS174T cells were injected into null mice subcutaneously, followed by treatment with cetuximab, trastuzumab and T-DM1. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 at a dose of 300 mg/kg via IP injection.
In Vivo Model	LS174T CDX model
In Vitro Model	Colon adenocarcinoma	LS174T cells		CVCL_1384
Experiment 21 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 66.70%	Low HER2 expression (HER2+)
Method Description	Subcutaneous injection of 100,000 cells mixed in 200 mL PBS solution was performed. Two weeks after tumour cell injection, mice were treated with trastuzumab, cetuximab or T-DM1 (30 mg/kg, once per week i.p.) for 8 weeks.
In Vivo Model	HCC827 CDX model
In Vitro Model	Lung adenocarcinoma	HCC827 cells		CVCL_2063
Experiment 22 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 74%	High HER2 expression (HER2+++)
Method Description	The activity of trastuzumab-MCC-DM1 was further investigated in trastuzumab-insensitive mouse xenograft model. After transplantation of MMTV-HER2 Fo5 mammary tumor explants, tumor-bearing nude mice (n = 8 mice per group) were treated once every 3 weeks with 10 mg/kg trastuzmab-MCC-DM1.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 23 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 76.54%	Positive HER2 expression (HER2+++/++)
Method Description	Inoculate 150 mice with KPL-4 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (1 mg/kg) via the tail vein on Day 0.    Click to Show/Hide
In Vivo Model	KPL-4 CDX model
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 24 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.90%	Positive HER2 expression (HER2+++/++)
Method Description	Inoculate 150 mice with KPL-4 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (ADC-211, 1 mg/kg plus ADC-106, 5 mg/kg) via the tail vein on Day 0.    Click to Show/Hide
In Vivo Model	KPL-4 CDX model
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 25 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.90%	High HER2 expression (HER2+++)
Method Description	Mice bearing mammary tumor transplants from the MMTV-HER2 Fo5 line were given a single iv injection (10 mg/kg) of Tmab-SPP-DM1, Tmab-SSNPP-DM3, Tmab-SSNPP-DM4, Tmab-MCC-DM1, or vehicle (n=7 mice per group), and tumor growth was monitored for 25 days.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 26 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 84.39%	Positive HER2 expression (HER2+++/++)
Method Description	Inoculate 150 mice with KPL-4 cells at 3 million cells/mouse suspended in HBSS/matrigel, in the thoracic mammary fat pad at a volume of 0.2 ml. When tumors have reached a mean tumor volume of 100-250 mm3, they will be grouped out into 10 groups of 8-10 mice each. A single treatment will be administered intravenously (ADC-211, 1 mg/kg plus ADC-106, 1 mg/kg) via the tail vein on Day 0.    Click to Show/Hide
In Vivo Model	KPL-4 CDX model
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 27 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.70%	High HER2 expression (HER2+++)
Method Description	The activity of trastuzumab-MCC-DM1 was further investigated in trastuzumab-insensitive mouse xenograft model. After transplantation of MMTV-HER2 Fo5 mammary tumor explants, tumor-bearing nude mice (n = 8 mice per group) were treated once every 3 weeks with 15 mg/kg trastuzmab-MCC-DM1.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 28 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.10%	High HER2 expression (HER2+++)
Method Description	The activity of trastuzumab-MCC-DM1 was further investigated in trastuzumab-insensitive mouse xenograft model. After transplantation of MMTV-HER2 Fo5 mammary tumor explants, tumor-bearing nude mice (n = 8 mice per group) were treated once every 3 weeks with 30 mg/kg trastuzmab-MCC-DM1.
In Vivo Model	MMTV-HER2 Fo5 CDX model (Trastuzumab resistant)
In Vitro Model	Breast cancer	MMTV-HER2 cells		Mus musculus
Experiment 29 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.70%	High HER2 expression (HER2+++)
Method Description	Naive female beige nude XID mice were inoculated in the mammary fat pad with 20 million tumor cells suspended in 50% phenol redfree Matrigel mixed with culture medium. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Nude mice with established tumors were dosed i.v. with Tmab-MCC-DM1 10 mg/kg for a total of three injections.    Click to Show/Hide
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 30 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.30%	High HER2 expression (HER2+++)
Method Description	KPL-4 human breast tumor cells were inoculated (3 million cells per mouse, in Matrigel) into the mammary fat pads of SCID beige mice. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Trastuzumab-maytansinoid conjugates were given by single 15 mg/kg iv injection.
In Vivo Model	Breast cancer CDX model
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 31 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.70%	High HER2 expression (HER2+++)
Method Description	Naive female beige nude XID mice were inoculated in the mammary fat pad with 20 million tumor cells suspended in 50% phenol redfree Matrigel mixed with culture medium. All animals were randomly assigned into treatment groups, such that the mean tumor volume for each group was 100 to 200 mm3. Nude mice with established tumors were dosed i.v. with Tmab-MCC-DM1 15 mg/kg for a total of three injections.    Click to Show/Hide
In Vivo Model	Trastuzumab-resistant breast cancer CDX model
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 32 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.40%	High HER2 expression (HER2+++)
Method Description	The antitumor activity of T-DM1 was evaluated in various mice xenograft models with different HER2 expression levels; KPL-4 (strong positive). Each cell suspension or tumor fragment was inoculated subcutaneously into specific pathogen-free female nude mice.The tumor-bearing mice were randomized into treatment and control groups based on the tumor volumes, and dosing was initiated on day 0. In this group, 10 mg/kg T-DM1 was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	KPL-4 cell line xenograft model
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 33 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High HER2 expression (HER2+++)
Method Description	Mice were inoculated subcutaneously in the right flank with either 5x106 cells/mouse of BTC cell line KKU-100, mice were randomized to the control group or treatment with T-DM1 20 mg/kg groups.
In Vivo Model	KMCH-1 CDX model
In Vitro Model	Combined hepatocellular carcinoma and cholangiocarcinoma	KMCH-1 cells		CVCL_7970
Experiment 34 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Positive HER2 expression (HER2 +++/++)
Method Description	HER2-positive HCC1954 cells were either treated with vehicle (control) or T-DM1 for 5 days, trypsinized, washed in PBS and sorted by flow cytometry based on the surface ROR1 expression. ROR1- and ROR1+ or unfractionated cells were injected into the subcutaneous site of 6-8-week old Nu/J mice (n=3/group).
In Vivo Model	HCC1954 CDX model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 35 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Minimal Effective Dose (MED)	< 5 mg/kg	Moderate HER2 expression (HER2++)
Method Description	Following the acclimatization period (1 week), the animals were stratified by body weight and randomly assigned to the following group: two T-DM1 groups, treated with 20 mg/kg and 60 mg/kg. Each group consisted of five animals for blood chemistry test as well as five animals for clinical signs and body weight measurements.
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 36 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Maximum Tolerated Dose (MTD)	> 20 mg/kg	High HER2 expression (HER2+++)
Method Description	Following the acclimatization period (1 week), the animals were stratified by body weight and randomly assigned to the following group: two T-DM1 groups, treated with 20 mg/kg and 60 mg/kg. Each group consisted of five animals for blood chemistry test as well as five animals for clinical signs and body weight measurements.
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.98%	High HER2 expression (HER2 +++)
Method Description	An allograft was propagated from the Fo5 mmty transgenic mouse which does not respond to.or responds poorly to HERCEPTIN therapy. Subjects were treated once with ADC (10 mg/kg); and placebo PBS buffer control (Vehicle) andmonitored over 3 weeks.
In Vivo Model	Breast cancer model MMTV-HER2 Fo5

Experiment 1 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.04 nM	High HER2 expression (HER2 +++)
Method Description	With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.14 nM	High HER2 expression (HER2 +++)
Method Description	With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[26]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.24 nM	High HER2 expression (HER2 +++)
Method Description	To determine the IC50 values of the ADCs, different concentrations of each conjugate was directly added to the culture medium. After the cells were cultured for 3 days at 37°C, the number of viable cells was quantified by using the WST- reagent, and the absorbance was measured at OD450.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 4 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.24 nM	Low HER2 expression (HER2+; IHC 1+)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. For measurement of apoptosis, BT-474 and SK-BR-3 were exposed to trastuzumab or trastuzumab-DM for 48 h.    Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 5 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.26 nM	High HER2 expression (HER2 +++)
Method Description	With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 6 Reporting the Activity Date of This ADC					[26]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.57 nM	High HER2 expression (HER2 +++)
Method Description	To determine the IC50 values of the ADCs, different concentrations of each conjugate was directly added to the culture medium. After the cells were cultured for 3 days at 37°C, the number of viable cells was quantified by using the WST- reagent, and the absorbance was measured at OD450.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 7 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.76 nM	Moderate HER2 expression (HER2 ++)
Method Description	With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 8 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.71 nM
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. For measurement of apoptosis, BT-474 and SK-BR-3 were exposed to trastuzumab or trastuzumab-DM for 48 h.    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 9 Reporting the Activity Date of This ADC					[26]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.89 nM	High HER2 expression (HER2 +++)
Method Description	To determine the IC50 values of the ADCs, different concentrations of each conjugate was directly added to the culture medium. After the cells were cultured for 3 days at 37°C, the number of viable cells was quantified by using the WST- reagent, and the absorbance was measured at OD450.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 10 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	6.4 nM	Positive HER2 expression (HER2 +++/++)
Method Description	ADCs 21-23 was performed on HCC827 and NCI-H2228 cells. cells (5 x 103 cells/well) were cultured in 96-well plates with 100 uL complete medium, and 24 h later the cells were treated in triplicate with varying concentrations of ADCs for 72 h.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 11 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	18.37 nM	Low HER2 expression (HER2+; IHC 1+)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 12 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 50 nM	Negative HER2 expression (HER2 -)
Method Description	With OHPAS ADCs 1-4 , we first performed cell-based MTT assays against a series of HER2 positive/negative cell lines using the commercially available HER2 ADC, T-DM1 (average DAR 3.5), which we purchased as a positive control.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 13 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative HER2 expression (HER2 -)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 14 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	220 nM	Negative HER2 expression (HER2 -)
Method Description	ADCs 21-23 was performed on HCC827 and NCI-H2228 cells. cells (5 x 103 cells/well) were cultured in 96-well plates with 100 uL complete medium, and 24 h later the cells were treated in triplicate with varying concentrations of ADCs for 72 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 15 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	317 nM	Negative HER2 expression (HER2 -)
Method Description	ADCs 21-23 was performed on HCC827 and NCI-H2228 cells. cells (5 x 103 cells/well) were cultured in 96-well plates with 100 uL complete medium, and 24 h later the cells were treated in triplicate with varying concentrations of ADCs for 72 h.
In Vitro Model	Lung adenocarcinoma	HCC827 cells		CVCL_2063
Experiment 16 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 500 nM	Negative HER2 expression (HER2 -)
Method Description	ADCs 21-23 was performed on HCC827 and NCI-H2228 cells. cells (5 x 103 cells/well) were cultured in 96-well plates with 100 uL complete medium, and 24 h later the cells were treated in triplicate with varying concentrations of ADCs for 72 h.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 17 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.00-15.00 ng/mL	High HER2 expression (HER2+++)
Method Description	Exposing mammalian cells having HER2 receptors to ADC in a cell culture medium; culturing the cells for a period from about 6 hours to about 5 days; and measuring cell viability Cell-based in vitro assays were used to measure viability, cytotoxicity, and induction of apoptosis of the ADC of the invention.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 18 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0 ug/mL	Negative HER2 expression (HER2-)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma of no special type	BT-474 EEI cells		CVCL_AR96
Experiment 19 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.01 ug/mL	Positive HER2 expression (HER2+++/++; HER2 MFI=95.7)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 20 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.01 ug/mL	Moderate HER2 expression (HER2++; IHC 2+)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 21 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.03 ug/mL	High HER2 expression (HER2+++)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 22 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.06 ug/mL	High HER2 expression (HER2+++)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 23 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.27 ug/mL	Low HER2 expression (HER2+)
Method Description	The effects of trastuzumab and trastuzumab-maytansinoid conjugates on tumor cell viability were assessed using Cell Titer-Glo. Cells were plated in black-walled 96-well plates (20,000 per well for BT-474; 10,000 cells per well for all other lines) and allowed to adhere overnight at 37°C in a humidified atmosphere of 5% CO2. Medium was then removed and replaced by fresh culture medium containing different concentrations of trastuzumab, trastuzumab ADC, or free DM1, and the cells incubated for varying periods of time.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	MKN7 cells		CVCL_1417

Ref 1	Trastuzumab emtansine: first global approval
Ref 2	Semi-mechanistic population pharmacokinetic model of multivalent trastuzumab emtansine in patients with metastatic breast cancer
Ref 3	Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates
Ref 4	A mechanistic pharmacokinetic model elucidating the disposition of trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) for treatment of metastatic breast cancer
Ref 5	Phase I and pharmacokinetic study of trastuzumab emtansine in Japanese patients with HER2-positive metastatic breast cancer
Ref 6	A Phase I Pharmacokinetic Study of Trastuzumab Emtansine (T-DM1) in Patients with Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer and Normal or Reduced Hepatic Function
Ref 7	An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer
Ref 8	Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial. Ann Oncol. 2020 Oct;31(10):1350-1358. doi: 10.1016/j.annonc.2020.06.020.
Ref 9	Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma. Cancer Med. 2023 Jun;12(11):12071-12083. doi: 10.1002/cam4.5893. Epub 2023 Apr 29.
Ref 10	Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q. Ann Oncol. 2019 Nov 1;30(11):1821-1830. doi: 10.1093/annonc/mdz291.
Ref 11	Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020 Oct;21(10):1283-1295. doi: 10.1016/S1470-2045(20)30465-4.
Ref 12	Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. J Immunother Cancer. 2022 Oct;10(10):e005119.
Ref 13	Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. J Clin Oncol. 2022 Feb 10;40(5):438-448.
Ref 14	DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016 Oct 15;22(20):5097-5108.
Ref 15	Neutralization of BCL-2/X(L) Enhances the Cytotoxicity of T-DM1 In Vivo. Mol Cancer Ther. 2019 Jun;18(6):1115-1126. doi: 10.1158/1535-7163.MCT-18-0743. Epub 2019 Apr 8.
Ref 16	Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008 Nov 15;68(22):9280-90.
Ref 17	Application of trastuzumab emtansine in HER-2-positive and KRAS/BRAF-mutated colon cancer cells. Eur J Clin Invest. 2020 Apr 29:e13255. doi: 10.1111/eci.13255.
Ref 18	Beneficial effect of erlotinib and trastuzumab emtansine combination in lung tumors harboring EGFR mutations. Biochem Biophys Res Commun. 2020 Nov 12;532(3):341-346. doi: 10.1016/j.bbrc.2020.07.055.
Ref 19	YES1 amplification confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive cancer. Br J Cancer. 2020 Sep;123(6):1000-1011. doi: 10.1038/s41416-020-0952-1.
Ref 20	Pyrrolobenzodiazepine antibody drug conjugates and methods of use; 2017-04-06.
Ref 21	Molecular targeting of HER2-overexpressing biliary tract cancer cells with trastuzumab emtansine, an antibody-cytotoxic drug conjugate. Cancer Chemother Pharmacol. 2019 Apr;83(4):659-671. doi: 10.1007/s00280-019-03768-8. Epub 2019 Jan 18.
Ref 22	Antibody-drug conjugate T-DM1 treatment for HER2+ breast cancer induces ROR1 and confers resistance through activation of Hippo transcriptional coactivator YAP1. EBioMedicine. 2019 May;43:211-224. doi: 10.1016/j.ebiom.2019.04.061.
Ref 23	Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP. Front Biosci (Landmark Ed). 2022 Aug 5;27(8):234.
Ref 24	Cysteine engineered antibodies and conjugates.
Ref 25	Aryl Sulfate is a Useful Motif for Conjugating and Releasing Phenolic Molecules: Sulfur Fluorine Exchange Click Chemistry Enables Discovery of Ortho-Hydroxy-Protected Aryl Sulfate Linker. Bioconjug Chem. 2019 Jul 17;30(7):1957-1968. doi: 10.1021/acs.bioconjchem.9b00340. Epub 2019 Jun 28.
Ref 26	Preparation and characterization of antibody-drug conjugates acting on HER2-positive cancer cells. PLoS One. 2020 Sep 28;15(9):e0239813. doi: 10.1371/journal.pone.0239813. eCollection 2020.
Ref 27	Near-infrared-induced drug release from antibody-drug double conjugates exerts a cytotoxic photo-bystander effect. Bioeng Transl Med. 2022 Aug 21;7(3):e10388. doi: 10.1002/btm2.10388. eCollection 2022 Sep.