ADC ID	DRG0JEVIM
ADC Name	Disitamab vedotin
Brand Name	Aidixi
Synonyms	disitamab vedotin; hertuzumab-vc-MMAE; RC48-ADC; aidixi; veldicitumab; RC48; vedicitumab    Click to Show/Hide
Organization	RemeGen (Originator);Seagen (Top20 MNC)
Drug Status	Approved in 2021
Drug-to-Antibody Ratio	4
Structure
				2D MOL
Antibody Name	Hertuzumab					Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)					Antigen Info
Payload Name	MMAE					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	Mc-Val-Cit-PABC					Linker Info
Conjugate Type	Random Cysteines
Combination Type	vedotin
Absorption	Serum concentrations of disitamab vedotin increase rapidly after intravenous infusion, with maximum concentrations of MMAE-bound antibody and total antibody attained before and after the infusion ends [2]. Serum concentrations of free MMAE peak ≈ 2 days after infusion, although exposure to free MMAE in serum was low in clinical studies. After repeat administration of disitamab vedotin 2.0 or 2.5 mg/kg every 2 weeks, MMAE-bound antibody and free MMAE do not accumulate.
Distribution	The apparent volume of distribution of MMAE-bound antibody at steady state is 124.7-340.8 mL/kg and that of total antibody is 72.1-87.2 mL/kg (average values); population pharmacokinetic analysis suggests that MMAE has apparent distribution volumes of 29.0 and 59.3 L in the central and peripheral compartments
Metabolism	Metabolism of MMAE occurs mainly via CYP3A4/5, although may also occur via CYP2D6. After single doses of 2.0 or 2.5 mg/kg, the half-lives of MMAE-bound antibody are 33.1 and 45.7 h and those of free MMAE are 66.5 and 64.0 h; the respective serum clearance rates for MMAE-bound antibody are 2.8 and 2.4 mL/h/kg
Special Approval(s)	Breakthrough therapy (FDA); Fast track (FDA); Orphan drug (FDA); Conditional marketing authorisation (NMPA); Priority review (NMPA)

Dissocation Constant (Kd)	Binding Target	Description	Reference
0.5 nM	HER2	Disitamab Vedotin (RC48) is an ADC with a higher affinity for HER2 than the targeted drug trastuzumab (KD, 5.0E-10M vs KD, 1.9E-09M)	[1]

Bystander Killing Effect	Description	Reference
yes	the proposed mechanism of action (MOA) of DV occurs through direct cytotoxicity of HER2-expressing tumor cells following internalization of DV and intracellular release of MMAE. DV may also induce antitumor activity through bystander-mediated cytotoxicity of neighboring cells and via the inhibition of HER2 signaling pathways.    Click to Show/Hide	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	66.07	ug/mL	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Maximum Observed Concentration (Cmax)	142.39	ug/mL	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Maximum Observed Concentration (Cmax)	259.2	ug/mL	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	1179.48	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	2227.16	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	5725.56	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Maximum Observed Concentration (Cmax)	8911.59	ng/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	17895.71	ng/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	38833.71	ng/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	33988.74	ng/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	51822.75	ng/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	127540.78	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	238733.48	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460847.62	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	724141.06	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1118314.75	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	3862.58	ng/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	22495.4	ng/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	26736.66	ng/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	52698.97	ng/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Maximum Observed Concentration (Cmax)	51192.24	ng/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	405764.85	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460866.73	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	827377.82	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1110759.12	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]

Standard Type	Value	Units	Description	Reference
Volume of Distribution (Vd)	124.73-340.8	mL/kg	The apparent volume of distribution of MMAE-bound antibody at steady state is 124.7-340.8 mL/kg and that of total antibody is 72.1-87.2 mL/kg (average values)	[1]
Area Under the Concentration-Time Curve (AUC)	1179.48	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	2227.16	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	5725.56	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Volume of Distribution (Vd)	0.1218	L/kg	Mouse PK Parameters, ADC volume of distribution for central compartment	[3]
Volume of Distribution (Vd)	0.1499	L/kg	Mouse PK Parameters, ADC volume of distribution for peripheral compartmen	[3]
Volume of Distribution (Vd)	0.039	L/kg	Monkey PK, ADC volume of distribution for central compartment	[3]
Volume of Distribution (Vd)	0.0154	L/kg	Monkey PK, ADC volume of distribution for peripheral compartment	[3]
Volume of Distribution (Vd)	0.039	L/kg	Predicted human PK, ADC volume of distribution for central compartment	[3]
Volume of Distribution (Vd)	0.0154	L/kg	Predicted human PK, ADC volume of distribution for peripheral compartment	[3]
Area Under the Concentration-Time Curve (AUC)	127540.78	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	238733.48	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460847.62	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	724141.06	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1118314.75	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	405764.85	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460866.73	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	827377.82	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1110759.12	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Volume of Distribution (Vd)	0.1218	L/kg	Mouse PK Parameters, ADC volume of distribution for central compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.1499	L/kg	Mouse PK Parameters, ADC volume of distribution for peripheral compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.039	L/kg	Monkey PK, ADC volume of distribution for central compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.0154	L/kg	Monkey PK, ADC volume of distribution for peripheral compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.039	L/kg	Predicted human PK, ADC volume of distribution for central compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.0154	L/kg	Predicted human PK, ADC volume of distribution for peripheral compartment: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	1179.48	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	2227.16	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	5725.56	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	127540.78	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	238733.48	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460847.62	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	724141.06	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1118314.75	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	405764.85	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460866.73	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	827377.82	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1110759.12	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]

Standard Type	Value	Units	Description	Reference
Clearance (CL)	2.8	mL/h/kg	After single doses of 2.0 mg/kg, the half-lives of MMAE-bound antibody are 33.1 and 45.7 h and those of free MMAE are 66.5 and 64.0 h; the respective serum clearance rates for MMAE-bound antibody are 2.8 and 2.4 mL/h/kg    Click to Show/Hide	[1]
Clearance (CL)	2.4	mL/h/kg	After single doses of 2.5 mg/kg, the half-lives of MMAE-bound antibody are 33.1 and 45.7 h and those of free MMAE are 66.5 and 64.0 h; the respective serum clearance rates for MMAE-bound antibody are 2.8 and 2.4 mL/h/kg    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	33.1	h	After single doses of 2.0 mg/kg, the half-lives of MMAE-bound antibody are 33.1 and 45.7 h and those of free MMAE are 66.5 and 64.0 h; the respective serum clearance rates for MMAE-bound antibody are 2.8 and 2.4 mL/h/kg    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	45.7	h	After single doses of 2.5 mg/kg, the half-lives of MMAE-bound antibody are 33.1 and 45.7 h and those of free MMAE are 66.5 and 64.0 h; the respective serum clearance rates for MMAE-bound antibody are 2.8 and 2.4 mL/h/kg    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	0.5	h	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Elimination Half-Life (t1/2)	0.5	h	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Elimination Half-Life (t1/2)	0.5	h	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	1179.48	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (3 mg/kg, n=6), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	2227.16	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (6 mg/kg, n=10), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Area Under the Concentration-Time Curve (AUC)	5725.56	ug*h/mL	After monkeys were intravenously infused with Disitamab vedotin (12 mg/kg, n=14), the exposure levels of ADC was positively correlated with the dose and basically a linear pharmacokinetic profile was noted.    Click to Show/Hide	[2]
Clearance (CL)	0.0026	L/h/kg	Mouse PK Parameters, Plasma clearance of ADC	[3]
Clearance (CL)	0.009	L/h/kg	Mouse PK Parameters, Distribution clearance of ADC	[3]
Clearance (CL)	0.0016	L/h/kg	Monkey PK, Plasma clearance of ADC	[3]
Clearance (CL)	0.0023	L/h/kg	Monkey PK, Distribution clearance of ADC	[3]
Clearance (CL)	0.0016	L/h/kg	Predicted human PK, Plasma clearance of ADC	[3]
Clearance (CL)	0.0023	L/h/kg	Predicted human PK, Distribution clearance of ADC	[3]
Elimination Half-Life (t1/2)	17.38	h	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Elimination Half-Life (t1/2)	20.87	h	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Elimination Half-Life (t1/2)	31.48	h	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Elimination Half-Life (t1/2)	30.73	h	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Elimination Half-Life (t1/2)	32.71	h	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	127540.78	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 0.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	238733.48	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460847.62	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	724141.06	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1118314.75	ng*h/mL	PK parameters of disitamab vedotin in patients after a single administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Elimination Half-Life (t1/2)	16.32	h	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Elimination Half-Life (t1/2)	26.42	h	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Elimination Half-Life (t1/2)	33.56	h	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Elimination Half-Life (t1/2)	38.88	h	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	405764.85	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	460866.73	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 1.5 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	827377.82	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2 mg/kg.	[4]
Area Under the Concentration-Time Curve (AUC)	1110759.12	ng*h/mL	PK parameters of disitamab vedotin in patients after multiple administration in the C001 CANCER and C003 CANCER studies, 2.5 mg/kg.	[4]
Clearance (CL)	0.0026	L/h/kg	Mouse PK Parameters, Plasma clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Clearance (CL)	0.009	L/h/kg	Mouse PK Parameters, Distribution clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Clearance (CL)	0.0016	L/h/kg	Monkey PK, Plasma clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Clearance (CL)	0.0023	L/h/kg	Monkey PK, Distribution clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Clearance (CL)	0.0016	L/h/kg	Predicted human PK Plasma clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]
Clearance (CL)	0.0023	L/h/kg	Predicted human PK, Distribution clearance of ADC: The total antibody, conjugated antibody and payload were characterized by a two-compartment linear model. The conjugated antibody released into the central compartment through elimination and nonspecific dissociation (Kdec).    Click to Show/Hide	[3]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT04714190	Phase 3	Randomized, controlled, multicenter phase 1/2 clinical study evaluating the efficacy and safety of RC48-ADC for the treatment of locally advanced or metastatic gastric cancer with HER2-overexpression.
Objective Response Rate (ORR)	NCT03556345	Phase 2	A multicenter, open label single arm, phase 2 study to evaluate the effect and safety of recombinant humanized anti-HER2 monoclonal antibody-mmae conjugate for injection in HER2 overexpressing local advanced or metastatic gastric cancer.    Click to Show/Hide
Objective Response Rate (ORR)	NCT02881190	Phase 1	A tolerance, safety and pharmacokinetic ascending dose phase 1 study of RC48-ADC administered intravenously to subjects with HER2-positive malignant in advanced malignant solid tumors.
Objective Response Rate (ORR)	NCT04264936	Phase 1	A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.
Objective Response Rate (ORR)	NCT04264936	Phase 1	A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 61.2	%	Gastric cancer PDX model (PDX: Model6)
Tumor Growth Inhibition value (TGI)	≈ 64.5	%	Gastric cancer PDX model (PDX: Model8)
Tumor Growth Inhibition value (TGI)	≈ 70.8	%	Gastric cancer PDX model (PDX: Model9)
Tumor Growth Inhibition value (TGI)	≈ 81.8	%	Gastric cancer PDX model (PDX: Model3)
Tumor Growth Inhibition value (TGI)	≈ 89.6	%	Gastric cancer PDX model (PDX: Model5)
Tumor Growth Inhibition value (TGI)	≈ 94	%	Gastric cancer PDX model (PDX: Model7)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Gastric cancer PDX model (PDX: Model4)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Gastric cancer PDX model (PDX: Model2)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Gastric cancer PDX model (PDX: Model1)

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	90	ng/mL	EO771 cells	Mammary gland malignant neoplasms
Half Maximal Inhibitory Concentration (IC50)	0.8	ug/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.3	ug/mL	SNU-216 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	3.8	ug/mL	NUGC-4 cells	Gastric signet ring cell adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	52.4	ug/mL	HGC-27 cells	Gastric carcinoma

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	4.91	ng/mL	SK-BR-3 cells	Breast adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	11.28	ng/mL	SK-OV-3 cells	Ovarian serous cystadenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	14.54	ng/mL	NCI-N87 cells	Gastric tubular adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Objective Response Rate (ORR)	24.80%	High HER2 expression (HER2+++; IHC 3+)
Patients Enrolled	Locally advanced or metastatic gastric cancer with HER2-overexpression.
Administration Dosage	2.50 mg/kg IV every 2 weeks.
Related Clinical Trial
NCT Number	NCT04714190	Clinical Status	Phase 3
Clinical Description	Randomized, controlled, multicenter phase 1/2 clinical study evaluating the efficacy and safety of RC48-ADC for the treatment of locally advanced or metastatic gastric cancer with HER2-overexpression.
Primary Endpoint	The ORR was 24.80% (95% confidence interval [CI]: 17.50%-33.30%).
Other Endpoint	The median PFS and OS were 4.10 months (95% CI: 3.70-4.90 months) and 7.90 months (95% CI: 6.70-9.90 months), respectively. The most frequently reported adverse events were decreased white blood cell count (53.60%), asthenia (53.60%), hair loss (53.60%), decreased neutrophil count (52.00%), anemia (49.60%), and increased aspartate aminotransferase level (43.20%). Serious adverse events (SAEs) occurred in 45 (36.00%) patients, and RC48-related SAEs were mainly decreased neutrophil count (3.20%). Seven patients had adverse events that led to death were not RC48-related.    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Objective Response Rate (ORR)	24.80%	High HER2 expression (HER2+++; IHC 3+)
Patients Enrolled	HER2overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least secondline therapy.
Administration Dosage	2.50 mg/kg alone by intravenous infusion during 30-90 min (60 min is recommended) every two weeks.
Related Clinical Trial
NCT Number	NCT03556345	Clinical Status	Phase 2
Clinical Description	A multicenter, open label single arm, phase 2 study to evaluate the effect and safety of recombinant humanized anti-HER2 monoclonal antibody-mmae conjugate for injection in HER2 overexpressing local advanced or metastatic gastric cancer.
Primary Endpoint	The ORR was 24.80% (95% confidence interval [CI]: 17.50%-33.30%).
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Objective Response Rate (ORR)	21.05 35.71 20.00 13.64 15.00 %
Patients Enrolled	Patients with incurable, locally advanced or metastatic solid cancers were eligible for inclusion if their tumors showed HER2 protein overexpression by IHC (3+or 2+), regardless of whether FISH was positive or negative.
Administration Dosage	0.10 mg/kg, 0.50 mg/kg, 1.00 mg/kg, 1.50 mg/kg, 2.00 mg/kg, 2.50 mg/kg, 3.00 mg/kg, 3.50 mg/kg, and 4.00 mg/kg; Q3W; dose expansion proceeded at the dose of 2.00 mg/kg Q2W.
Related Clinical Trial
NCT Number	NCT02881190	Clinical Status	Phase 1
Clinical Description	A tolerance, safety and pharmacokinetic ascending dose phase 1 study of RC48-ADC administered intravenously to subjects with HER2-positive malignant in advanced malignant solid tumors.
Primary Endpoint	The MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D.
Other Endpoint	ORR and DCR were 21.05% (12/57) and 49.12% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+and IHC3+, with ORRs of 35.71% (5/14), 20.00% (2/10), and 13.64% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efcacy, with ORR of 15.00% (3/20) and DCR of 45.00% (9/20).    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Objective Response Rate (ORR)	51.20%
Patients Enrolled	Advanced or metastatic urothelial cancer.
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT04264936	Clinical Status	Phase 1
Clinical Description	A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.
Primary Endpoint	The overall confirmed ORR as assessed by the BIRC was 51.20% (95% CI: 35.50%, 66.70%).
Other Endpoint	For RC48-ADC at 2.00 mg/kg, The median PFS and OS were 6.90 months (95% CI: 5.60, 8.90) and 13.90 months (95% CI: 9.10, NE), respectively.
Experiment 5 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Objective Response Rate (ORR)	80.00 75.00 100.00 77.80 66.70 50.00 97.10 50.00 %
Patients Enrolled	HER2-positive and even negative patients (pts) with metastatic urothelial carcinoma (mUC).
Administration Dosage	1.50 or 2.00 mg/kg RC48-ADC + 3 mg/kg toripalimab with the traditional 3+3 escalation design. In the expansion cohort, patients received the recommended dose of RC48-ADC + toripalimab every 2 weeks. The primary endpoints were safety/tolerability and recommended RC48-ADC dose.
Related Clinical Trial
NCT Number	NCT04264936	Clinical Status	Phase 1
Clinical Description	A open-label, single-arm, phase 1b/2 study of RC48-ADC and JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer.
Primary Endpoint	At data cutoff, confirmed investigator-assessed ORR=75.00% (95%CI: 50.90-91.30), including 15.00% CRs; DCR=95.00% (95%CI: 75.10-99.90).
Other Endpoint	The ORR for 1L previously untreated mUC pts was 80.00%. The ORR for pts with liver mets was 75.00%. The ORR was 100.00% for pts with HER2 (3+), 77.80% for HER2 (2+), 66.70% for HER2 (1+), and 50.00% for HER2 (0) respectively. The ORR was 97.10% in pts with PD-L1 CPS1 and 50.00% in CPS < 1.

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.20%	Moderate HER2 expression (HER2++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model6)
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 64.50%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model8)
Experiment 3 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 70.80%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model9)
Experiment 4 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 81.80%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model3)
Experiment 5 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.60%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model5)
Experiment 6 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94%	High HER2 expression (HER2+++; IHC 3+)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model7)
Experiment 7 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate HER2 expression (HER2++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model4)
Experiment 8 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model2)
Experiment 9 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 22 days.
In Vivo Model	Gastric cancer PDX model (PDX: Model1)

Experiment 1 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	90 ng/mL	Low HER2 expression (HER2+; IHC 1+)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with PBS, ADC (5 mg/kg), PD-1 antibody (10 mg/kg), or their combination (ADC+PD-1 antibody or ADC+PD-L1 antibody) for 10 days.
In Vivo Model	Triple-negative breast cancer cell line E0771-hHER2 xenograft model
In Vitro Model	Mammary gland malignant neoplasms	EO771 cells		CVCL_GR23
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.8 ug/mL	High HER2 expression (HER2+++)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.3 ug/mL	High HER2 expression (HER2+++; IHC 3+)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model	Gastric tubular adenocarcinoma	SNU-216 cells		CVCL_3946
Experiment 4 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.8 ug/mL	Moderate HER2 expression (HER2++; IHC 2+)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model	Gastric signet ring cell adenocarcinoma	NUGC-4 cells		CVCL_3082
Experiment 5 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	52.4 ug/mL	Moderate HER2 expression (HER2++; IHC 2+)
Method Description	The inhibitory activity of RC48 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated with RC48 for 72 h.
In Vitro Model	Gastric carcinoma	HGC-27 cells		CVCL_1279

Experiment 1 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.91 ng/mL	High HER2 expression (HER2+++)
Method Description	To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.28 ng/mL	High HER2 expression (HER2+++)
Method Description	To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14.54 ng/mL	High HER2 expression (HER2+++)
Method Description	To test the anti-tumor effect of single drug, SK-BR-3, NCI-N87 and SK-OV-3 cells were selected for viability analysis following 72 h incubation with or without RC48ADC which was dispersed in a concentration gradient.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Ref 1	Disitamab Vedotin: First Approval
Ref 2	Preclinical safety profile of disitamab vedotin:a novel anti-HER2 antibody conjugated with MMAE
Ref 3	Towards a platform quantitative systems pharmacology (QSP) model for preclinical to clinical translation of antibody drug conjugates (ADCs)
Ref 4	Disitamab vedotin, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpression and HER2-low advanced breast cancer: a phase I/Ib study
Ref 5	Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study. Cancer Commun (Lond). 2021 Nov;41(11):1173-1182.
Ref 6	Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Gastric Cancer. 2021 Jul;24(4):913-925.
Ref 7	A Open-label, Single-arm, Phase Ib/II Study of RC48-ADC and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer, NCT04264936
Ref 8	Preliminary results of RC48-ADC combined with toripalimab in patients with locally advanced or metastatic urothelial carcinoma. Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022) 515-515.
Ref 9	From AVATAR Mice to Patients: RC48-ADC Exerted Promising Efficacy in Advanced Gastric Cancer With HER2 Expression. Front Pharmacol. 2022 Jan 5;12:757994.
Ref 10	A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+tumors in hPD-1 transgenic mouse model and contributes immune memory formation. Breast Cancer Res Treat. 2022 Jan;191(1):51-61.
Ref 11	Proton pump inhibitors interfere with the anti-tumor potency of RC48ADC. Toxicol In Vitro. 2022 Mar;79:105292.