ADC ID	DRG0ERKBH
ADC Name	Trastuzumab deruxtecan
Brand Name	Enhertu
Synonyms	trastuzumab deruxtecan; DS-8201; fam-trastuzumab deruxtecan-nxki; Enhertu; trastuzumab deruxtecan-nxki; DS-8201a; T-DXd    Click to Show/Hide
Organization	Daiichi Sankyo (Originator);AstraZeneca (Top20 MNC)
Drug Status	Approved in 2019
Drug-to-Antibody Ratio	8
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	DXd					Payload Info
Therapeutic Target	DNA topoisomerase 1 (TOP1)					Target Info
Linker Name	Mc-Gly-Gly-Phe-Gly					Linker Info
Conjugate Type	Random Cysteines
Combination Type	deruxtecan
Absorption	For trastuzumab deruxtecan (5.4 mg/kg), Cmax was 122 ug/mL (20%), AUC was 735 ug day/mL (31%).
Distribution	The estimated volume of distribution of trastuzumab deruxtecan in the central compartment is 2.77 L. Pharmacokinetic studies found that the unchanged drug is distributed in the blood and is not significantly retained in tissues. The Dxd portion of the drug has a plasma protein binding estimated at 97%.
Metabolism	Trastuzumab deruxtecan undergoes catabolic breakdown into small peptides and amino acids, akin to the natural metabolism of endogenous IgG. The peptide linker connecting the topoisomerase I inhibitor and the antibody is believed to be cleaved by Cathepsin B and L enzymes. In vitro, the topoisomerase inhibitor component, DXd, demonstrates metabolism by the CYP3A4 enzyme. The median elimination half-life of trastuzumab deruxtecan was 5.8 days.
Toxicity	Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with trastuzumab deruxtecan
Special Approval(s)	Priority review (FDA); Accelerated approval (FDA); Fast track (FDA); Orphan drug (FDA); Breakthrough therapy (FDA); Priority review (NMPA); Breakthrough therapy (NMPA)

Bystander Killing Effect	Description	Reference
yes	Preclinical in-vitro and in-vivo studies suggest that trastuzumab deruxtecan has a potent cytotoxic bystander effect, by contrast with trastuzumab emtansine, DS-8201a kills both HER2-positive and HER2-negative cells under coculture conditions    Click to Show/Hide	[1]

Dissocation Constant (Kd)	Binding Target	Description	Reference
7.3 ng/mL	HER2	The Kd values of the antibody and DS-8201a for the HER2 ECD protein were 7.8 ng/ml and 7.3 ng/ ml, respectively.	[1]

Incubation Time	21days	Release	4%	Reference	[1]
Incubation Medium	cynomolgus monkey plasma
Description	the linker of DS-8201a was stable, which was consistent with the fact that only 4% of DXd was released even after 21 days of in vitro incubation of DS-8201a in cynomolgus monkey plasma.

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	133	ug/mL	At the recommended dosage of ENHERTU for patients with metastatic breast cancer, the geometric mean (coefficient of variation [CV]%) Cmax of fam-trastuzumab deruxtecan-nxki was 133 ug/mL (19%).	[1]
Area Under the Concentration-Time Curve (AUC)	780	day*ug/mL	At the recommended dosage of ENHERTU for patients with metastatic breast cancer, the AUC of fam-trastuzumab deruxtecan-nxki was 780 ug·day/mL.	[1]
Area Under the Concentration-Time Curve (AUC)	1.87±0.487	day*ug/mL	PK parameters of 0.1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	8.43±0.859	day*ug/mL	PK parameters of 0.3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3	[2]
Area Under the Concentration-Time Curve (AUC)	46.1±4.52	day*ug/mL	PK parameters of 1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	216±20.7	day*ug/mL	PK parameters of 3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	670±97	day*ug/mL	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	1.96	uM*day	Following a 10 mg/kg IV dose, test in Capan-1 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.75	uM*day	Following a 10 mg/kg IV dose, test in JIMT-1 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.48	uM*day	Following a 10 mg/kg IV dose, test in MDA-MB-468 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	0.2	uM*day	Following a 1 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.4	uM*day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Maximum Observed Concentration (Cmax)	133	ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) .	[4]
Maximum Observed Concentration (Cmax)	139	ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) .	[4]
Area Under the Concentration-Time Curve (AUC)	650	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	701	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	644	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under plasma concentration-time curve over dosing interval.	[4]
Area Under the Concentration-Time Curve (AUC)	706	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under plasma concentration-time curve over dosing interval.	[4]
Maximum Observed Concentration (Cmax)	179	ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,.	[6]
Maximum Observed Concentration (Cmax)	154	ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	905	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3, area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to the last quantifiable time.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	731	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to infinity.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	623	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 2, area under the concentration-time curve from cycle day 1-17.	[7]
Area Under the Concentration-Time Curve (AUC)	742	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 3, area under the concentration-time curve from cycle day 1-17.	[7]
Maximum Observed Concentration (Cmax)	131	ug/mL	330P Pharmacokinetics of T-DXd, cycle 2.	[7]
Maximum Observed Concentration (Cmax)	138	ug/mL	330P Pharmacokinetics of T-DXd, cycle 3.	[7]
Area Under the Concentration-Time Curve (AUC)	318±19	day*ug/mL	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	780	day*ug/mL	At the recommended dosage of ENHERTU for patients with metastatic breast cancer, the AUC of fam-trastuzumab deruxtecan-nxki was 780 ug·day/mL.	[1]
Volume of Distribution (Vd)	75.2	mL/kg	At the recommended dose of 5.4 mg/kg, the volume of distribution at steady state was 75.2 ml/kg	[1]
Area Under the Concentration-Time Curve (AUC)	1.87±0.487	day*ug/mL	PK parameters of 0.1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	8.43±0.859	day*ug/mL	PK parameters of 0.3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3	[2]
Area Under the Concentration-Time Curve (AUC)	46.1±4.52	day*ug/mL	PK parameters of 1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	216±20.7	day*ug/mL	PK parameters of 3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	670±97	day*ug/mL	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Volume of Distribution (Vd)	45.3±6.73	mL/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Volume of Distribution (Vd)	30.6±3.89	mL/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Volume of Distribution (Vd)	55.4±2.61	mL/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Volume of Distribution (Vd)	52.7±11.3	mL/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Volume of Distribution (Vd)	60.8±5.8	mL/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	1.96	uM*day	Following a 10 mg/kg IV dose, test in Capan-1 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.75	uM*day	Following a 10 mg/kg IV dose, test in JIMT-1 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.48	uM*day	Following a 10 mg/kg IV dose, test in MDA-MB-468 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	0.2	uM*day	Following a 1 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.4	uM*day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Volume of Distribution (Vd)	79.5	mL/kg	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Volume of Distribution (Vd)	105.5	mL/kg	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Volume of Distribution (Vd)	99.6	mL/kg	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Volume of Distribution (Vd)	123.7	mL/kg	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Volume of Distribution (Vd)	146.3	mL/kg	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	650	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	701	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	644	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under plasma concentration-time curve over dosing interval.	[4]
Area Under the Concentration-Time Curve (AUC)	706	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under plasma concentration-time curve over dosing interval.	[4]
Volume of Distribution (Vd)	72	mL/kg	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) .	[4]
Volume of Distribution (Vd)	71.9	mL/kg	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) .	[4]
Volume of Distribution (Vd)	2.78	L	In the final PopPK model, the pharmacokinetic profile of T-DXd was adequately described by a 2-compartment model with linear elimination, and the pharmacokinetic profile of DXd was described as a 1-compartment model with a 2-component, time-varying release rate from T-DXd. Central volume of distribution    Click to Show/Hide	[5]
Volume of Distribution (Vd)	4.98	L	In the final PopPK model, the pharmacokinetic profile of T-DXd was adequately described by a 2-compartment model with linear elimination, and the pharmacokinetic profile of DXd was described as a 1-compartment model with a 2-component, time-varying release rate from T-DXd. Peripheral volume of distribution.    Click to Show/Hide	[5]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	905	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3, area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to the last quantifiable time.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	731	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to infinity.    Click to Show/Hide	[6]
Volume of Distribution (Vd)	60.9	mL/kg	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,.	[6]
Volume of Distribution (Vd)	66.3	mL/kg	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	623	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 2, area under the concentration-time curve from cycle day 1-17.	[7]
Area Under the Concentration-Time Curve (AUC)	742	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 3, area under the concentration-time curve from cycle day 1-17.	[7]
Volume of Distribution (Vd)	2.77	L	Parameter estimates from the final population pharmacokinetics model for intact trastuzumab deruxtecan, Central volume of distribution	[8]
Volume of Distribution (Vd)	5.16	L	Parameter estimates from the final population pharmacokinetics model for intact trastuzumab deruxtecan, Peripheral volume of distribution.	[8]
Area Under the Concentration-Time Curve (AUC)	318±19	day*ug/mL	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]
Volume of Distribution (Vd)	87±4.8	mL/kg	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	780	day*ug/mL	At the recommended dosage of ENHERTU for patients with metastatic breast cancer, the AUC of fam-trastuzumab deruxtecan-nxki was 780 ug·day/mL.	[1]
Area Under the Concentration-Time Curve (AUC)	1.87±0.487	day*ug/mL	PK parameters of 0.1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	8.43±0.859	day*ug/mL	PK parameters of 0.3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3	[2]
Area Under the Concentration-Time Curve (AUC)	46.1±4.52	day*ug/mL	PK parameters of 1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	216±20.7	day*ug/mL	PK parameters of 3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	670±97	day*ug/mL	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	1.96	uM*day	Following a 10 mg/kg IV dose, test in Capan-1 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.75	uM*day	Following a 10 mg/kg IV dose, test in JIMT-1 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.48	uM*day	Following a 10 mg/kg IV dose, test in MDA-MB-468 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	0.2	uM*day	Following a 1 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.4	uM*day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	650	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	701	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	644	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under plasma concentration-time curve over dosing interval.	[4]
Area Under the Concentration-Time Curve (AUC)	706	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under plasma concentration-time curve over dosing interval.	[4]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	905	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3, area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to the last quantifiable time.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	731	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to infinity.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	623	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 2, area under the concentration-time curve from cycle day 1-17.	[7]
Area Under the Concentration-Time Curve (AUC)	742	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 3, area under the concentration-time curve from cycle day 1-17.	[7]
Area Under the Concentration-Time Curve (AUC)	318±19	day*ug/mL	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	5.8	days	In a pharmacokinetic study, the median elimination half-life of trastuzumab deruxtecan was about 5.8 days.	[1]
Clearance (CL)	0.42	L/day	Trastuzumab deruxtecan is rapidly cleared from systemic circulation. Estimated systemic clearance of trastuzumab deruxtecan is 0.42 L/day, according to a population pharmacokinetic analysis. DXd showed a systemic clearance of about 19.2 L/h    Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	780	day*ug/mL	At the recommended dosage of ENHERTU for patients with metastatic breast cancer, the AUC of fam-trastuzumab deruxtecan-nxki was 780 ug·day/mL.	[1]
Area Under the Concentration-Time Curve (AUC)	1.87±0.487	day*ug/mL	PK parameters of 0.1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	8.43±0.859	day*ug/mL	PK parameters of 0.3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3	[2]
Area Under the Concentration-Time Curve (AUC)	46.1±4.52	day*ug/mL	PK parameters of 1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	216±20.7	day*ug/mL	PK parameters of 3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	670±97	day*ug/mL	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Elimination Half-Life (t1/2)	0.641±0.137	days	PK parameters of 0.1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Elimination Half-Life (t1/2)	0.686±0.191	days	PK parameters of 0.3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3	[2]
Elimination Half-Life (t1/2)	2.90±0.0829	days	PK parameters of 1 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Elimination Half-Life (t1/2)	3.92±1.71	days	PK parameters of 3 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Elimination Half-Life (t1/2)	4.54±0.48	days	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Clearance (CL)	55.7±13.4	mL/day/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Clearance (CL)	35.9±3.78	mL/day/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Clearance (CL)	21.8±2.27	mL/day/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Clearance (CL)	14.0±1.35	mL/day/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Clearance (CL)	12.2±1.7	mL/day/kg	PK parameters of 8 mg/kg DS-8201a following iv administration of DS-8201a to monkeys (N = 3)	[2]
Area Under the Concentration-Time Curve (AUC)	1.96	uM*day	Following a 10 mg/kg IV dose, test in Capan-1 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.75	uM*day	Following a 10 mg/kg IV dose, test in JIMT-1 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.48	uM*day	Following a 10 mg/kg IV dose, test in MDA-MB-468 NOD-SCID mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	0.2	uM*day	Following a 1 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	2.4	uM*day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Elimination Half-Life (t1/2)	1.5	days	Following a 10 mg/kg IV dose, test in Capan-1 NOD-SCID mouse.	[3]
Elimination Half-Life (t1/2)	3.4	days	Following a 10 mg/kg IV dose, test in JIMT-1 Nude mouse.	[3]
Elimination Half-Life (t1/2)	3.2	days	Following a 10 mg/kg IV dose, test in MDA-MB-468 NOD-SCID mouse.	[3]
Elimination Half-Life (t1/2)	2.9	days	Following a 1 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Elimination Half-Life (t1/2)	4.5	days	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Clearance (CL)	33.2	mL/kg/day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Clearance (CL)	23.7	mL/kg/day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Clearance (CL)	26.2	mL/kg/day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Clearance (CL)	32.5	mL/kg/day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Clearance (CL)	26.6	mL/kg/day	Following a 10 mg/kg IV dose, test in NCI-N87 Nude mouse.	[3]
Area Under the Concentration-Time Curve (AUC)	650	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	701	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under the serum concentration-time curve through day 17 of cycle.	[4]
Area Under the Concentration-Time Curve (AUC)	644	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) , area under plasma concentration-time curve over dosing interval.	[4]
Area Under the Concentration-Time Curve (AUC)	706	day*ug/mL	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) , area under plasma concentration-time curve over dosing interval.	[4]
Elimination Half-Life (t1/2)	7.19	days	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) .	[4]
Elimination Half-Life (t1/2)	7.13	days	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) .	[4]
Clearance (CL)	8.22	mL/day/kg	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 1) .	[4]
Clearance (CL)	8.39	mL/day/kg	Pharmacokinetics of T-DXd in patients receiving T-DXd alone (cycle 2, cohort 2) .	[4]
Clearance (CL)	0.42	L/d	In the final PopPK model, the pharmacokinetic profile of T-DXd was adequately described by a 2-compartment model with linear elimination, and the pharmacokinetic profile of DXd was described as a 1-compartment model with a 2-component, time-varying release rate from T-DXd.    Click to Show/Hide	[5]
Clearance (CL)	0.198	L/d	In the final PopPK model, the pharmacokinetic profile of T-DXd was adequately described by a 2-compartment model with linear elimination, and the pharmacokinetic profile of DXd was described as a 1-compartment model with a 2-component, time-varying release rate from T-DXd. Distributional clearance.    Click to Show/Hide	[5]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	905	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3, area under the serum concentration-time curve during the dosing interval.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	677	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to the last quantifiable time.    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	731	day*ug/mL	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1, area under the serum concentration-time curve up to infinity.    Click to Show/Hide	[6]
Elimination Half-Life (t1/2)	5.82	day	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,.	[6]
Elimination Half-Life (t1/2)	7.4	day	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3    Click to Show/Hide	[6]
Clearance (CL)	9.18	mL/day/kg	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1,.	[6]
Clearance (CL)	7.4	mL/day/kg	Pharmacokinetics parameters for T-DXd, all 51 patients (Pharmacokinetics Analysis Set; cutoff date of December 5, 2018) were included in the analysis for cycle 1 and of 47 patients still on treatment at cycle 3    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	623	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 2, area under the concentration-time curve from cycle day 1-17.	[7]
Area Under the Concentration-Time Curve (AUC)	742	day*ug/mL	330P Pharmacokinetics of T-DXd, cycle 3, area under the concentration-time curve from cycle day 1-17.	[7]
Clearance (CL)	0.421	L/d	Parameter estimates from the final population pharmacokinetics model for intact trastuzumab deruxtecan	[8]
Clearance (CL)	0.199	L/d	Parameter estimates from the final population pharmacokinetics model for intact trastuzumab deruxtecan, Distributional clearance	[8]
Area Under the Concentration-Time Curve (AUC)	318±19	day*ug/mL	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]
Elimination Half-Life (t1/2)	8.23±1.39	day	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]
Clearance (CL)	7.92±0.83	mL/day/kg	Pharmacokinetic parameters of total Ab and T-DXd after a single iv administration of T-DXd at 3 mg/kg in mice (N = 3, mean ± SD).	[9]

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal inhibitory Concentration (IC50)Human PBMC	0.0652	nM	CVCL_0033	Breast adenocarcinoma
Half Maximal inhibitory Concentration (IC50)Human PBMC	0.2344	nM	CVCL_1603	Gastric tubular adenocarcinoma
Half Maximal inhibitory Concentration (IC50)Human PBMC	> 100	nM	CVCL_2077	Breast ductal carcinoma
Half Maximal inhibitory Concentration (IC50)Human PBMC	> 100	nM	CVCL_0031	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	0.7	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	4.8	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	5.1	ng/mL	MDA-MB-453 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	5.3	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	6.1	ng/mL	MDA-MB-453 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	6.7	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	7.6	ng/mL	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	7.6	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	8.1	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	9	ng/mL	MDA-MB-453 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	11.5	ng/mL	MDA-MB-453 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	15.1	ng/mL	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	15.7	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	24.9	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	25.4	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	26.8	ng/mL	KPL-4 cells	Breast inflammatory carcinoma
Half Maximal Inhibitory Concentration (IC50)	32.7	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	34.8	ng/mL	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	41.7	ng/mL	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	41.8	ng/mL	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	MDA-MB-231 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	MDA-MB-231 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	MDA-MB-231 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	MDA-MB-231 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 3000	ng/mL	BT-474 cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	3	ug/mL	HCT 116-H2H cells (High HER2 expression)	Colon carcinoma
Half Maximal Inhibitory Concentration (IC50)	> 10	ug/mL	MDA-MB-468 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	97	ug/mL	NCI-N87 cells	Gastric tubular adenocarcinoma

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT03734029	Phase 3	A phase 3, multicenter, randomized, open-label, active controlled trial of DS-8201a, an Anti-HER2-antibody drug conjugate (ADC), versus treatment of physician's choice for HER2-low, unresectable and/or metastatic breast cancer subjects.    Click to Show/Hide
Objective Response Rate (ORR)	NCT03529110	Phase 3	A phase 3, multicenter, randomized, open-label, active-controlled study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 antibody drug conjugate (ADC), versus Ado Trastuzumab Emtansine (T-DM1) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.    Click to Show/Hide
Objective Response Rate (ORR)	NCT03529110	Phase 3	A phase 3, multicenter, randomized, open-label, active-controlled study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 antibody drug conjugate (ADC), versus Ado Trastuzumab Emtansine (T-DM1) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.    Click to Show/Hide
Objective Response Rate (ORR)	NCT03329690	Phase 2	A phase 2, multicenter, open-label study of DS-8201a in subjects with HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma.
Objective Response Rate (ORR)	NCT04744831	Phase 2	A phase 2, multicenter, randomized, study of trastuzumab deruxtecan in participants with HER2-overexpressing locally advanced, unresectable or metastatic colorectal cancer (DESTINY-CRC02).
Objective Response Rate (ORR)	NCT03505710	Phase 2	A phase 2, multicenter, open-label, 2-cohort study of Trastuzumab Deruxtecan (DS-8201a), an anti-HER2 antibody drug conjugate (ADC), for HER2-over-expressing or -mutated, unresectable and/or metastatic non small cell lung cancer (NSCLC) (DESTINY-Lung01).    Click to Show/Hide
Objective Response Rate (ORR)	NCT04644237	Phase 2	A phase 2, multicenter, randomized study of trastuzumab deruxtecan in subjects with HER2-mutated metastatic non-small cell lung cancer (NSCLC) (DESTINY-LUNG02).
Objective Response Rate (ORR)	NCT03248492	Phase 2	A phase 2, multicenter, open-label study of DS-8201a, an anti-HER2-antibody drug conjugate (ADC) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with T-DM1 (DESTINY-Breast01).    Click to Show/Hide
Objective Response Rate (ORR)	NCT04752059	Phase 2	Phase 2 study of trastuzumab-deruxtecan (T-DX; DS-8201a) in HER2-positive breast cancer patients with newly diagnosed or progressing brain metastases.
Objective Response Rate (ORR)	NCT02564900	Phase 1	Phase 1, two-part, multicenter, non-randomized, open-label, multiple dose first-in-human study of DS-8201A, in subjects with advanced solid malignant tumors.
Objective Response Rate (ORR)	Undisclosed	Undisclosed	Trastuzumab deruxtecan 6.40 or 5.40 mg/kg was administered intravenously once every 3 weeks until unacceptable toxicity or disease progression Dose modification was based on the updatedrecommended phase 2 dose for breast cancer to be 5.4 mg/kg.    Click to Show/Hide

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 88.9	%	Gastric cancer PDX model (PDX: NIBIO G016)
Tumor Growth Inhibition value (TGI)	≈ 96.3	%	Breast cancer PDX model (PDX: ST313)
Tumor Growth Inhibition value (TGI)	≈ 98.2	%	Breast cancer PDX model (PDX: ST565)
Tumor Growth Inhibition value (TGI)	≈ 98.6	%	Breast cancer PDX model (PDX: ST225)

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 0	%	HCT 116-Mock cells (Negative HER2 expression)	Colon carcinoma
Tumor Growth Inhibition value (TGI)	≈ 13.5	%	CFPAC-1 cells	Pancreatic ductal adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 17.2	%	GCIY cells	Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 28.8	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 58.5	%	JIMT-1 cells	Breast ductal carcinoma
Tumor Growth Inhibition value (TGI)	≈ 61.6	%	Capan-1 cells	Pancreatic ductal adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 62.5	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 66.7	%	EMT6 cells (High HER2 expression)	Mammary gland malignant neoplasms
Tumor Growth Inhibition value (TGI)	≈ 68.7	%	HCT 116-H2L cells (Low HER2 expression)	Colon carcinoma
Tumor Growth Inhibition value (TGI)	≈ 86	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 88.3	%	KPL-4 cells	Breast inflammatory carcinoma
Tumor Growth Inhibition value (TGI)	≈ 96.1	%	HCT 116-H2H cells (High HER2 expression)	Colon carcinoma
Tumor Growth Inhibition value (TGI)	≈ 97.3	%	NCI-N87 cells	Gastric tubular adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 99.1	%	NCI-N87 cells	Gastric tubular adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal inhibitory Concentration (IC50)Human PBMC	0.0652 nM	Positive HER2 expression (HER2 +++/++)
Method Description	After sample addition, culture for 6 days. Thaw the CellTiter-Glo® reagent and place the cell culture plate at room temperature to equilibrate for 30 minutes. Then add 50 to each well. Shake and lyse the cell plate in a shaker for 2 minutes, then incubate at room temperature for 10 minutes to stabilize the luminescence signal.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal inhibitory Concentration (IC50)Human PBMC	0.2344 nM	High HER2 expression (HER2+++; >300,000 HER2 molecules/cell)
Method Description	After sample addition, culture for 6 days. Thaw the CellTiter-Glo® reagent and place the cell culture plate at room temperature to equilibrate for 30 minutes. Then add 50 to each well. Shake and lyse the cell plate in a shaker for 2 minutes, then incubate at room temperature for 10 minutes to stabilize the luminescence signal.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal inhibitory Concentration (IC50)Human PBMC	> 100 nM	Positive HER2 expression (HER2 +++/++)
Method Description	After sample addition, culture for 6 days. Thaw the CellTiter-Glo® reagent and place the cell culture plate at room temperature to equilibrate for 30 minutes. Then add 50 to each well. Shake and lyse the cell plate in a shaker for 2 minutes, then incubate at room temperature for 10 minutes to stabilize the luminescence signal.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 4 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal inhibitory Concentration (IC50)Human PBMC	> 100 nM	Negative HER2 expression (HER2-)
Method Description	After sample addition, culture for 6 days. Thaw the CellTiter-Glo® reagent and place the cell culture plate at room temperature to equilibrate for 30 minutes. Then add 50 to each well. Shake and lyse the cell plate in a shaker for 2 minutes, then incubate at room temperature for 10 minutes to stabilize the luminescence signal.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 5 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.7 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 6 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.8 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 7 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.1 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-453 cells		CVCL_0418
Experiment 8 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.3 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 9 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	6.1 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-453 cells		CVCL_0418
Experiment 10 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	6.7 ng/mL
Method Description	The inhibitory activity of DS-8201a against cancer cell growth was compared with an anti-HER2 Ab and control IgG-ADC-conjugated with DXd against various human cancer cell lines in vitroThe cells were treated with DS-8201a, anti-HER2 Ab, and control IgG-ADC for 6 days.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 11 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.6 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor BAY1895344 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 12 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.6 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor BAY1895344 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 13 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.1 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor BAY1898344 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 14 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor BAY1895344 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-453 cells		CVCL_0418
Experiment 15 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.5 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-453 cells		CVCL_0418
Experiment 16 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	15.1 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor BAY1895344 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 17 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	15.7 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 18 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.9 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 19 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	25.4 ng/mL
Method Description	The inhibitory activity of DS-8201a against cancer cell growth was compared with an anti-HER2 Ab and control IgG-ADC-conjugated with DXd against various human cancer cell lines in vitroThe cells were treated with DS-8201a, anti-HER2 Ab, and control IgG-ADC for 6 days.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 20 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	26.8 ng/mL
Method Description	The inhibitory activity of DS-8201a against cancer cell growth was compared with an anti-HER2 Ab and control IgG-ADC-conjugated with DXd against various human cancer cell lines in vitroThe cells were treated with DS-8201a, anti-HER2 Ab, and control IgG-ADC for 6 days.
In Vitro Model	Breast inflammatory carcinoma	KPL-4 cells		CVCL_5310
Experiment 21 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	32.7 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 22 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	34.8 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 23 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	41.7 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 24 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	41.8 ng/mL	Moderate HER2 expression (HER2 ++)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 25 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	Negative HER2 expression (HER2 -)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 and ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 26 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	Negative HER2 expression (HER2 -)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 27 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus ATR inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 28 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	Negative HER2 expression (HER2 -)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 29 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of DS-8201 plus PARP inhibitor AZD2281 against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 30 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	Negative HER2 expression (HER2 -)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 31 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 3000 ng/mL	High HER2 expression (HER2 +++)
Method Description	In vitro cytotoxicity of ADCs against a panel of multiple human cancer cell lines. IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 32 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3 ug/mL	High HER2 expression (HER2 +++, IHC 3+)
Method Description	Viability of NCI-N87 cells as well as of parental HCT116 cells and their derivatives (Mock, H2L and H2H) after incubation with the indicated concentrations of trastuzumab deruxtecan (DS-8201a) or T-DM1 for 144 h.
In Vitro Model	Colon carcinoma	HCT 116-H2H cells (High HER2 expression)		CVCL_0291
Experiment 33 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10 ug/mL
Method Description	The inhibitory activity of DS-8201a against cancer cell growth was compared with an anti-HER2 Ab and control IgG-ADC-conjugated with DXd against various human cancer cell lines in vitroThe cells were treated with DS-8201a, anti-HER2 Ab, and control IgG-ADC for 6 days.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 34 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	97 ug/mL	High HER2 expression (HER2 +++)
Method Description	Viability of NCI-N87 cells as well as of parental HCT116 cells and their derivatives (Mock, H2L and H2H) after incubation with the indicated concentrations of trastuzumab deruxtecan (DS-8201a) or T-DM1 for 144 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Objective Response Rate (ORR)	52.90 52.30 %
Patients Enrolled	HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy.
Administration Dosage	Intravenously every 3 weeks at a dose of 5.40 mg per kilogram of body weight.
Related Clinical Trial
NCT Number	NCT03734029	Clinical Status	Phase 3
Clinical Description	A phase 3, multicenter, randomized, open-label, active controlled trial of DS-8201a, an Anti-HER2-antibody drug conjugate (ADC), versus treatment of physician's choice for HER2-low, unresectable and/or metastatic breast cancer subjects.
Primary Endpoint	In HR+ cohort, for ENHERTU (N=331), median Progression-Free Survival (mFPS)=10.10 months (95% Cl 9.50-11.50), for Chemotherapy (N=163), median Progression-Free Survival (mFPS)=5.40 months(95% Cl 4.40-7.10), hazard radio=0.51 (95% Cl 0.40-0.64) and p-value<0.0001.
Other Endpoint	In HR+ cohort, for ENHERTU (N=331), median overall survival (months)=23.90 (95% Cl 20.80-24.80), Confirmed Objective Response Rate=52.90% (95% Cl 47.30-58.40), Complete Response rate=36.00%, Partial Response rate= 49.50%, median Duration of Response (months)=10.70 (95% Cl 8.50-13.70); for Chemotherapy (N=163), median overall survival (months)=17.50 (95% Cl 15.20-24.80), Confirmed Objective Response Rate=16.60% (95% Cl 11.20-23.20), Complete Response rate=0.60%, Partial Response rate= 16.00%, median Duration of Response (months)=6.80 (95% Cl 6.50-9.90). In HR+ and HR- cohort, for ENHERTU (N=373), median Progression-Free Survival (mFPS)=9.90 months (95% Cl 9.00-11.30), median overall survival (months) = 23.40 (95% Cl 20.00-24.80), Confirmed Objective Response Rate = 52.30% (95% Cl 47.10-57.40), Complete Response rate=35.00%, Partial Response rate= 49.10%, median Duration of Response(months)=10.70 (95% Cl 8.50-13.20); for Chemotherapy (N=184), median Progression-Free Survival (mFPS)=5.40 months(95% Cl 4.20-6.80), median overall survival (months)=16.80(95% Cl 14.50-20.00), Confirmed Objective Response Rate=16.30% (95% Cl 11.30-22.50), Complete Response rate=11.00%, Partial Response rate= 15.20%, median Duration of Response(months)=6.80 (95% Cl 6.00-9.90).    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Objective Response Rate (ORR)	79.70%
Patients Enrolled	HER2-positive unresectable or metastatic breast cancer who were previously treated with trastuzumab and a taxane in the advanced or metastatic setting.
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT03529110	Clinical Status	Phase 3
Clinical Description	A phase 3, multicenter, randomized, open-label, active-controlled study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 antibody drug conjugate (ADC), versus Ado Trastuzumab Emtansine (T-DM1) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.
Primary Endpoint	The median patient age was 54 years. Approximately 50% of patients were treated with 0-1 prior lines of therapy in the metastatic setting, and 50% were treated with 2 prior treatment regimens. At baseline, 16.50% of patients in the T-DXd group and 14.80% of those in the T-DM1 group had brain metastases. At a median follow-up of 15.90 months, T-DXd significantly improved PFS by 72% compared with T-DM1 across all patient subgroups. Findings were consistent irrespective of hormone receptor status, prior treatment with pertuzumab, number of prior lines of therapy, presence or absence of visceral disease, and presence or absence of brain metastases. The overall response rate (ORR) in the overall study cohort was 79.70% and 34.20% in the T-DXd and T-DM1 groups, respectively, representing an absolute improvement in ORR of 45% with T-DXd Findings were consistent across all patient subgroups, with the absolute improvement in ORR associated with T-DXd relative to T-DM1 ranging from 39% to 52%.    Click to Show/Hide
Experiment 3 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Objective Response Rate (ORR)	79.70%
Patients Enrolled	HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.
Administration Dosage	Intravenously every 3 weeks at a dose of 5.40 mg per kilogram of body weigh.
Related Clinical Trial
NCT Number	NCT03529110	Clinical Status	Phase 3
Clinical Description	A phase 3, multicenter, randomized, open-label, active-controlled study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 antibody drug conjugate (ADC), versus Ado Trastuzumab Emtansine (T-DM1) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.
Primary Endpoint	For ENHERTU 5.40 mg/kg, Median Progression-Free Survival (mPFS)=not reached (95% Cl 18.5-not estimable); For Ado-trastuzumab emtansine 3.60 mg/kg, Median Progression-Free Survival (mPFS)=6.80months (95% Cl 5.60-8.20), hazard radio=0.28 (95% Cl 0.22-0.37) and p-value<0.0001.
Other Endpoint	For ENHERTU 5.40 mg/kg, Confirmed Objective Response Rate (ORR)=79.70% (95% Cl 74.30%-84.40%), complete response rate=16.10%, partial response rate=63.60%; For Ado-trastuzumab emtansine 3.60 mg/kg, Confirmed Objective Response Rate (ORR)=34.20% (95% Cl 28.50%-40.30%), complete response rate=8.70%, partial response rate=25.50%.
Experiment 4 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Objective Response Rate (ORR)	43%	Positive HER2 expression (HER2+++/++; HER2 MFI=562)
Patients Enrolled	HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab.
Administration Dosage	6.40 mg per kilogram of body weight every 3 weeks.
Related Clinical Trial
NCT Number	NCT03329690	Clinical Status	Phase 2
Clinical Description	A phase 2, multicenter, open-label study of DS-8201a in subjects with HER2-expressing advanced gastric or gastroesophageal junction adenocarcinoma.
Primary Endpoint	In the trastuzumab deruxtecan group, confirmed objective response rate=43.00% (95% Cl 34.00-52.00%), complete response rate=8.00%, partial response rate=34.00%. In the chemotherapy group, confirmed objective response rate=12.00% (95% Cl 5.00-24.00%), complete response rate=0.00%, partial response rate=12.00%.
Other Endpoint	In the trastuzumab deruxtecan group (N=119), confirmed disease control rate=86.00% (95% Cl 78.00-91.00%), median Duration of Response (mDOR)=11.30 months (95% Cl 5.60-not estimable), median overall survival (mOS)=12.50 months (95% Cl 9.60-14.30), estimated overall survival was 80.00% at 6 months and 52.00% at 12 months, median progression-free survival (mPFS)=5.60 months (95% CI, 4.30-6.90), estimated progression-free survival=43.00% at 6 months and 30.00% at 12 months In the chemotherapy group (N=56), confirmed disease control rate=62.00% (95% Cl 49.00-75.00%), median Duration of Response (mDOR)=3.90 months (95% Cl 3.0-4.9), median overall survival (mOS)=8.40 months (95% Cl 6.90-10.70), estimated overall survival was 66.00% at 6 months and 29.00% at 12 months, median progression-free survival (mPFS)=3.50 months (95% CI, 2.00-4.30), estimated progression-free survival=21.00% at 6 months and 0.00% at 12 months.    Click to Show/Hide
Experiment 5 Reporting the Activity Date of This ADC					[15]
Efficacy Data	Objective Response Rate (ORR)	45.30%	High HER2 expression (HER2 +++)
Patients Enrolled	86 patients with metastatic colorectal cancer (mCRC) were enrolled and received at least 1 dose of T-DXd, including 53 patients in cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+), 15 patients in cohort B (HER2 IHC 2+/ISH), and 18 patients in cohort C (HER2 IHC 1+).
Administration Dosage	6.4 mg/kg every 3 weeks
Related Clinical Trial
NCT Number	NCT04744831	Clinical Status	Phase 2
Clinical Description	A phase 2, multicenter, randomized, study of trastuzumab deruxtecan in participants with HER2-overexpressing locally advanced, unresectable or metastatic colorectal cancer (DESTINY-CRC02).
Primary Endpoint	ORR of 45.30% in cohort A
Other Endpoint	No responses occurred in cohorts B or C. Median progression-free survival, overall survival, and duration of response were 6.90, 15.50, and 7.00 months, respectively.
Experiment 6 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Objective Response Rate (ORR)	55%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Patients Enrolled	HER2-overexpressing or HER2-mutant non-small cell lung cancer (NSCLC).
Administration Dosage	Intravenously every 3 weeks at a dose of 6.40 mg per kilogram of body weight.
Related Clinical Trial
NCT Number	NCT03505710	Clinical Status	Phase 2
Clinical Description	A phase 2, multicenter, open-label, 2-cohort study of Trastuzumab Deruxtecan (DS-8201a), an anti-HER2 antibody drug conjugate (ADC), for HER2-over-expressing or -mutated, unresectable and/or metastatic non small cell lung cancer (NSCLC) (DESTINY-Lung01).
Primary Endpoint	Confirmed objective response rate=55.00% (95% CI, 44.00%-65.00%), confirmed complete response rate=1.00%, confirmed partial response=54.00%.
Other Endpoint	Median duration of response (mDOR) = 9.30 months (95% CI, 5.70-14.70), Median progression-free survival (mPFS) = 8.20 months (95% CI, 6.00-11.90), median overall survival=17.80 months (95% CI, 13.80-22.10).
Experiment 7 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Objective Response Rate (ORR)	57.70%	Negative HER2 expression (HER2-; HER2 MFI=10)
Patients Enrolled	HER2-mutated metastatic non-small cell lung cancer (NSCLC).
Administration Dosage	6.40 mg/kg administered by intravenous infusion every 3 weeks (Q3W).
Related Clinical Trial
NCT Number	NCT04644237	Clinical Status	Phase 2
Clinical Description	A phase 2, multicenter, randomized study of trastuzumab deruxtecan in subjects with HER2-mutated metastatic non-small cell lung cancer (NSCLC) (DESTINY-LUNG02).
Primary Endpoint	Confirmed Objective Response Rate=57.70% (95% CI, 43.20-71.30%), Complete Response rate=19.00%, Partial Response=55.80%.
Other Endpoint	Median Duration of Response (mDOR) = 8.70 months (95% Cl 7.10-not estimable).
Experiment 8 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Objective Response Rate (ORR)	60.90%	Positive HER2 expression (HER2+++/++; HER2 MFI=957)
Patients Enrolled	Pathologically documented HER2-positive, unresectable or metastatic breast cancer who had received previous treatment with trastuzumab emtansine.
Administration Dosage	5.4 mg per kilogram administered by intravenous infusion every 3 weeks.
Related Clinical Trial
NCT Number	NCT03248492	Clinical Status	Phase 2
Clinical Description	A phase 2, multicenter, open-label study of DS-8201a, an anti-HER2-antibody drug conjugate (ADC) for HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with T-DM1 (DESTINY-Breast01).
Primary Endpoint	Confirmed Objective Response Rate=60.90% (95% CI, 53.40%-68.00%), complete response rate=6.00%, partial response rate= 54.90%.
Other Endpoint	Disease-control rate was 97.30% (95% CI, 93.80-99.10), Median Duration of Response (months)=14.80 (95% CI, 13.80-16.90), clinical-benefit rate was 76.10% (95% CI, 69.30-82.10), median duration of progression-free survival was 16.40 months (95% CI, 12.70-not reached), estimated overall survival was 93.90% (95% CI, 89.30-96.60) at 6 months and 86.20% (95% CI, 79.80-90.70) at 12 months.    Click to Show/Hide
Experiment 9 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Objective Response Rate (ORR)	73.33%
Patients Enrolled	HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy.
Administration Dosage	5.40 mg per kg bodyweight once every 3 weeks intravenously.
Related Clinical Trial
NCT Number	NCT04752059	Clinical Status	Phase 2
Clinical Description	Phase 2 study of trastuzumab-deruxtecan (T-DX; DS-8201a) in HER2-positive breast cancer patients with newly diagnosed or progressing brain metastases.
Primary Endpoint	In the ITT population (n=15 patients), intracranial response rate by RANO-BM was 73.33% (95% CI 48.10-89.10%) (11/15 patients; 2 patients in complete remission (13.33%); 9 patients in partial remission (60.00%)). In the per protocol population (PP;n=14 patients), the response rate was 78.57% (95% CI 49.20-95.30%) (11/14). Two patients had stable disease for 6 months and one patient had stable disease at first restaging and progressed after four cycles of trastuzumab deruxtecan. Clinical benefit rate was 13/14 (92.86%; 95% CI 66.10-99.80%) in the PP population.    Click to Show/Hide
Other Endpoint	In patients with extracranial metastases at baseline (n=13), a partial response by RECIST 11 was observed in 5/13 (27.8%; 95% CI 13.9-68.4%) patients, with the remainder having stable disease. None of the patients progressing on trastuzumab deruxtecan had extracranial progression as the first site of progressive disease In patients with measurable extracranial disease at baseline (n=8), a partial remission was observed in 5/8 (62.50%; 95% CI 24.50-91.50%) patients, with the remainder having stable disease.    Click to Show/Hide
Experiment 10 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Objective Response Rate (ORR)	37%	Low HER2 expression (HER2 -)
Patients Enrolled	54 patients with HER2-low breast cancer
Administration Dosage	5.4 or 6.4 mg/kg.
Related Clinical Trial
NCT Number	NCT02564900	Clinical Status	Phase 1
Clinical Description	Phase 1, two-part, multicenter, non-randomized, open-label, multiple dose first-in-human study of DS-8201A, in subjects with advanced solid malignant tumors.
Primary Endpoint	Median duration of response = 10.40 months, median progression free survival (PFS) = 11.10 months, median overall survival = 29.40 months.
Other Endpoint	Confirmed ORR = 24.00 ; DOR, Median=11.00 months; TTR, months Median=2.80 ;PFS, months Median=8.00.
Experiment 11 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Objective Response Rate (ORR)	54.50 70.00 %
Patients Enrolled	Recurrent uterine carcinosarcoma (UCS) with HER2 immunohistochemistry scores 1+ previously treated with chemotherapy were included.
Administration Dosage	6.40 or 5.40 mg/kg was administered intravenously once every 3 weeks.

Experiment 1 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.90%	High HER2 expression (HER2+++; IHC 3+)
Method Description	The antitumor activity of DS-8201a 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, 3 mg/kg or 10 mg/kg DS-8201a was i.v. respectively to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX model (PDX: NIBIO G016)
Experiment 2 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.30%	Low HER2 expression (HER2+; IHC 1+)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a 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					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.20%	Low HER2 expression (HER2+; IHC 1+)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Breast cancer PDX model (PDX: ST565)
Experiment 4 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.60%	Moderate HER2 expression (HER2++; IHC 2+)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	Breast cancer PDX model (PDX: ST225)

Experiment 1 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0%	Negative HER2 expression (HER2 -)
Method Description	Volume of tumors formed by HCT116-Mock, HCT116-H2L or HCT116-H2H cells in nude mice injected intraperitoneally once every 3 weeks with PBS vehicle or trastuzumab deruxtecan (DS-8201a, 3 mg/kg) beginning at Day 0.
In Vivo Model	HCT116-Mock CDX model
In Vitro Model	Colon carcinoma	HCT 116-Mock cells (Negative HER2 expression)		CVCL_0291
Experiment 2 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 13.50%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of DS-8201a and trastuzumab were 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, 1 mg/kg DS-8201a or 10 mg/kg trastuzumab 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 3 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 17.20%	Negative HER2 expression (HER2-)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a or Anti-HER2 ADC(same drug-linker as DS-8201a and DAR=3.4) 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 4 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 28.80%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model. 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, 0.25 mg/kg DS-8201a was iv to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	HER2-positive NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 5 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 58.50%
Method Description	The antitumor activity of DS-8201a 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 DS-8201a or Anti-HER2 ADC(same drug-linker as DS-8201a and DAR=3.4) 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 6 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.60%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a or Anti-HER2 ADC(same drug-linker as DS-8201a and DAR=3.4) 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 7 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 62.50%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model. 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, 0.5 mg/kg DS-8201a was iv to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	HER2-positive NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 8 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 66.70%	Positive HER2 expression (HER2 +++/++)
Method Description	Trastuzumab deruxtecan (10 mg/kg, every seven days 2) induces efficient tumor cell killing in cell line-derived models of EMT6-hHER2 cells with HER2 expression with high expression.
In Vivo Model	EMT6 CDX model (Expressing hHER2)
In Vitro Model	Mammary gland malignant neoplasms	EMT6 cells (High HER2 expression)		CVCL_1923
Experiment 9 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.70%	Low HER2 expression (HER2 +, IHC 1+)
Method Description	Volume of tumors formed by HCT116-Mock, HCT116-H2L or HCT116-H2H cells in nude mice injected intraperitoneally once every 3 weeks with PBS vehicle or trastuzumab deruxtecan (DS-8201a, 3 mg/kg) beginning at Day 0.
In Vivo Model	HCT116-H2L CDX model
In Vitro Model	Colon carcinoma	HCT 116-H2L cells (Low HER2 expression)		CVCL_0291
Experiment 10 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model. 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, 1 mg/kg DS-8201a was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	HER2-positive NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 11 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.30%	Positive HER2 expression (HER2+++/++; HER2 MFI=95.7)
Method Description	The antitumor activity of DS-8201a 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 DS-8201a or Anti-HER2 ADC(same drug-linker as DS-8201a and DAR=3.4) 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 12 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.10%	High HER2 expression (HER2 +++, IHC 3+)
Method Description	Volume of tumors formed by HCT116-Mock, HCT116-H2L or HCT116-H2H cells in nude mice injected intraperitoneally once every 3 weeks with PBS vehicle or trastuzumab deruxtecan (DS-8201a, 3 mg/kg) beginning at Day 0.
In Vivo Model	HCT116-H2H CDX model
In Vitro Model	Colon carcinoma	HCT 116-H2H cells (High HER2 expression)		CVCL_0291
Experiment 13 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.30%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model. 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, 2 mg/kg DS-8201a was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	HER2-positive NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 14 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.10%	Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description	The in vivo antitumor activity of DS-8201a was evaluated in a HER2-positive NCI-N87 xenograft model. 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, 4 mg/kg DS-8201a was i.v. to the tumor-bearing mice.    Click to Show/Hide
In Vivo Model	HER2-positive NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Ref 1	Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer
Ref 2	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 3	Quantitative evaluation of trastuzumab deruxtecan pharmacokinetics and pharmacodynamics in mouse models of varying degrees of HER2 expression
Ref 4	Pharmacokinetics, Safety, and Efficacy of Trastuzumab Deruxtecan with Concomitant Ritonavir or Itraconazole in Patients with HER2-Expressing Advanced Solid Tumors
Ref 5	Trastuzumab Deruxtecan Dosing in Human Epidermal Growth Factor Receptor 2-Positive Gastric Cancer: Population Pharmacokinetic Modeling and Exposure-Response Analysis
Ref 6	Effect of Trastuzumab Deruxtecan on QT/QTc Interval and Pharmacokinetics in HER2-Positive or HER2-Low Metastatic/Unresectable Breast Cancer
Ref 7	330P - Pharmacokinetics (PK), safety, and efficacy of [fam-] trastuzumab deruxtecan with OATP1B/CYP3A inhibitors in subjects with HER2-expressing advanced solid tumours
Ref 8	Population Pharmacokinetics of Trastuzumab Deruxtecan in Patients With HER2-Positive Breast Cancer and Other Solid Tumors
Ref 9	Pharmacokinetics of trastuzumab deruxtecan (T-DXd), a novel anti-HER2 antibody-drug conjugate, in HER2-positive tumour-bearing mice
Ref 10	An antibody-drug conjugate and its uses
Ref 11	Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20.
Ref 12	Trastuzumab Deruxtecan Improves Progression-Free Survival and Intracranial Response in Patients with HER2-Positive Metastatic Breast Cancer and Brain Metastases. Oncologist. 2022 Mar 28;27(Suppl 1):S3-S4.
Ref 13	Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154.
Ref 14	Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430.
Ref 15	Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun. 2023 Jun 7;14(1):3332. doi: 10.1038/s41467-023-38032-4.
Ref 16	Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022 Jan 20;386(3):241-251.
Ref 17	Fam-trastuzumab deruxtecan-nxki for injection
Ref 18	Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020 Feb 13;382(7):610-621.
Ref 19	Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nat Med. 2022 Sep;28(9):1840-1847.
Ref 20	Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020 Jun 10;38(17):1887-1896. doi: 10.1200/JCO.19.02318. Epub 2020 Feb 14.
Ref 21	Trastuzumab Deruxtecan for Human Epidermal Growth Factor Receptor 2-Expressing Advanced or Recurrent Uterine Carcinosarcoma (NCCH1615): The STATICE Trial. J Clin Oncol. 2023 May 20;41(15):2789-2799.
Ref 22	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 23	[Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti-CTLA-4 antibody in a mouse model. PLoS One. 2019 Oct 1;14(10):e0222280. doi: 10.1371/journal.pone.0222280.
Ref 24	Combined inhibition of PARP and ATR synergistically potentiates the antitumor activity of HER2-targeting antibody-drug conjugate in HER2-positive cancers. Am J Cancer Res. 2023 Jan 15;13(1):161-175. eCollection 2023.