ADC Name	SHR-A1403
Synonyms	SHR-A1403; HTI-1403; HTI-1066    Click to Show/Hide
Organization	Jiangsu Hengrui Pharmaceuticals (Originator)
Drug Status	Phase 1 (discontinued)
Drug-to-Antibody Ratio	2
Structure
	3D MOL			2D MOL
Antibody Name	Anti-c-MET IgG2 mAb					Antibody Info
Antigen Name	Hepatocyte growth factor receptor (MET)					Antigen Info
Payload Name	SHR152852					Payload Info
Payload Target	Microtubule (MT)					Target Info
Linker Name	L2-MC					Linker Info
Conjugate Type	Undisclosed

Dissocation Constant (Kd)	Binding Target	Description	Reference
17.1 nM	Human cMet	In vitro binding affinity to c-Met protein derived from different species	[1]
31.9 nM	Cynomolgus monkey cMet	In vitro binding affinity to c-Met protein derived from different species	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	14.08	ug/mL	Serum exposure of SHR-A1403 in MKN-45 xenograft mice model following single intravenous injection, 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	937.72	ug·h/mL	Serum exposure of SHR-A1403 in MKN-45 xenograft mice model following single intravenous injection, 1 mg/kg, AUC0-168h.	[1]
Maximum Observed Concentration (Cmax)	49.93	ug/mL	Serum exposure of SHR-A1403 in MKN-45 xenograft mice model following single intravenous injection, 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	2663.07	ug·h/mL	Serum exposure of SHR-A1403 in MKN-45 xenograft mice model following single intravenous injection, 3 mg/kg, AUC0-168h.	[1]
Maximum Observed Concentration (Cmax)	11.9±4.18	ug/mL	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	49.8±6.65	ug/mL	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	19.6±1.88	ug/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	59.5±4.00	ug/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	162±18.6	ug/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 9 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	6.46±1.44	ug/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 0.3 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	28.3±2.20	ug/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	80.1±7.58	ug/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	953±65	ug·h/mL	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 1 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2686±218	ug·h/mL	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 3 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2050±152	ug·h/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 1 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	6390±889	ug·h/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 3 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	17500±1890	ug·h/mL	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 9 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	423±131	ug·h/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 0.3 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2640±554	ug·h/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 1 mg/kg, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	9220±1120	ug·h/mL	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 3 mg/kg, AUC0-t.	[2]
Maximum Observed Concentration (Cmax)	28.1	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 201.	[2]
Maximum Observed Concentration (Cmax)	24.6	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 202.	[2]
Maximum Observed Concentration (Cmax)	30.4	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 203.	[2]
Maximum Observed Concentration (Cmax)	29.8	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 211.	[2]
Maximum Observed Concentration (Cmax)	26.9	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 212.	[2]
Maximum Observed Concentration (Cmax)	29.7	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 213.	[2]
Maximum Observed Concentration (Cmax)	71.6	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 301.	[2]
Maximum Observed Concentration (Cmax)	75.9	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 302.	[2]
Maximum Observed Concentration (Cmax)	91.1	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 303.	[2]
Maximum Observed Concentration (Cmax)	84.2	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 311.	[2]
Maximum Observed Concentration (Cmax)	73.5	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 312.	[2]
Maximum Observed Concentration (Cmax)	84.1	ug/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 313.	[2]
Area Under the Concentration-Time Curve (AUC)	2320	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 201, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	1720	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 202, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2520	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 203, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	3210	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 211, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2820	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 212, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	2920	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 213, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	8450	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 301, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	9450	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 302, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	11000	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 303, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	7850	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 311, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	8850	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 312, AUC0-t.	[2]
Area Under the Concentration-Time Curve (AUC)	8890	ug·h/mL	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 313, AUC0-t.	[2]
Time to Maximum Concentration (Tmax)	0.5	h	Preliminary Pharmacokinetic Parameters of ABBV-011 ADC Following IV Infusion of ABBV-011 1 mg/kg in Cycle 1 (n=40)	[3]
Maximum Observed Concentration (Cmax)	24.2	ug/mL	Preliminary Pharmacokinetic Parameters of ABBV-011 ADC Following IV Infusion of ABBV-011 1 mg/kg in Cycle 1 (n=40)	[3]
Area Under the Concentration-Time Curve (AUC)	92.2	day·ug/mL	Preliminary Pharmacokinetic Parameters of ABBV-011 ADC Following IV Infusion of ABBV-011 1 mg/kg in Cycle 1 (n=40), AUC21d.	[3]

Standard Type	Value	Units	Description	Reference
Clearance (CL)	0.647	mL/h/kg	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Clearance (CL)	0.587	mL/h/kg	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Clearance (CL)	0.491±0.034	mL/h/kg	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Clearance (CL)	0.478±0.072	mL/h/kg	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Clearance (CL)	0.520±0.059	mL/h/kg	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 9 mg/kg.	[2]
Clearance (CL)	0.822±0.452	mL/h/kg	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 0.3 mg/kg.	[2]
Clearance (CL)	0.396±0.097	mL/h/kg	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Clearance (CL)	0.329±0.037	mL/h/kg	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Elimination Half-Life (t1/2)	132	h	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Elimination Half-Life (t1/2)	165	h	PK parameters of ADC in mice receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Elimination Half-Life (t1/2)	259±29.9	h	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Elimination Half-Life (t1/2)	259±39.9	h	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Elimination Half-Life (t1/2)	270±23.6	h	PK parameters of ADC in rat receiving single intravenous administration of SHR-A1403, 9 mg/kg.	[2]
Elimination Half-Life (t1/2)	111±39.3	h	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 0.3 mg/kg.	[2]
Elimination Half-Life (t1/2)	139±48.8	h	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 1 mg/kg.	[2]
Elimination Half-Life (t1/2)	156±29.5	h	PK parameters of ADC in monkey receiving single intravenous administration of SHR-A1403, 3 mg/kg.	[2]
Elimination Half-Life (t1/2)	136	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 201.	[2]
Elimination Half-Life (t1/2)	67	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 202.	[2]
Elimination Half-Life (t1/2)	104	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 203.	[2]
Elimination Half-Life (t1/2)	201	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 211.	[2]
Elimination Half-Life (t1/2)	179	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 212.	[2]
Elimination Half-Life (t1/2)	145	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 213.	[2]
Elimination Half-Life (t1/2)	187	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 301.	[2]
Elimination Half-Life (t1/2)	138	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 302.	[2]
Elimination Half-Life (t1/2)	176	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 303.	[2]
Elimination Half-Life (t1/2)	107	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 311.	[2]
Elimination Half-Life (t1/2)	172	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 312.	[2]
Elimination Half-Life (t1/2)	154	h	Individual PK parameters in monkeys receiving SHR-A1403 (DAR=2) at 1 mg/kg, monkey 313.	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT03856541	PHASE1	A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR-A1403 With Intravenous Infusion in Patients With Advanced Solid Tumors
Undisclosed	NCT03856541	Phase 1	A phase 1, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of SHR-a1403 with intravenous infusion in patients with advanced solid tumors.

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 95.5	%	Hepatic cancer PDX model (PDX: HCC)
Tumor Growth Inhibition value (TGI)	≈ 98.3	%	Hepatic cancer PDX model (PDX: HCC)
Tumor Growth Inhibition value (TGI)	≈ 98.5	%	Hepatic cancer PDX model (PDX: HCC)

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 0	%	HCC827 cells (Afatinib resistant HA1)	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 34.5	%	HCCLM3 cells	Adult hepatocellular carcinoma
Tumor Growth Inhibition value (TGI)	≈ 41.8	%	Lung cancer cells	Lung cancer
Tumor Growth Inhibition value (TGI)	≈ 42.8	%	Gastric cancer cells	Gastric cancer
Tumor Growth Inhibition value (TGI)	≈ 59.3	%	Lung cancer cells	Lung cancer
Tumor Growth Inhibition value (TGI)	≈ 83.3	%	HCCLM3 cells	Adult hepatocellular carcinoma
Tumor Growth Inhibition value (TGI)	≈ 84.6	%	MKN45 cells	Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 89.9	%	MKN45 cells	Gastric adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 91.6	%	NCI-H1993 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 92.8	%	HCC827 cells	Lung adenocarcinoma
Tumor Growth Inhibition value (TGI)	≈ 98.8	%	HCCLM3 cells	Adult hepatocellular carcinoma

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	3.2	ng/mL	HCCLM3 cells	Adult hepatocellular carcinoma
Half Maximal Inhibitory Concentration (IC50)	7.8	ng/mL	MKN45 cells	Gastric adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	11.8	ng/mL	HCC827 cells (Afatinib resistant HA1)	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	16.3	ng/mL	NCI-H1993 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	17.8	ng/mL	HCC827 cells (Gefitinib resistant)	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	26.6	ng/mL	HCC827 cells (Gefitinib resistant)	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	46.7	ng/mL	NCI-H441 cells	Lung papillary adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	53.9	ng/mL	Hs 578T cells	Invasive breast carcinoma
Half Maximal Inhibitory Concentration (IC50)	78.2	ng/mL	PC-3 cells	Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50)	99.4	ng/mL	HCC827 cells (Gefitinib resistant)	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	130.8	ng/mL	HCC827 cells (Gefitinib resistant)	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	214.8	ng/mL	Caki-1 cells	Clear cell renal cell carcinoma
Half Maximal Inhibitory Concentration (IC50)	918.9	ng/mL	HCC827 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1987.5	ng/mL	A-549 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 10	ug/mL	NCI-N87 cells	Gastric tubular adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	> 30	ug/mL	HCC827 cells (Afatinib resistant HA2)	Lung adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Eligible patients have ECOG 0-1, life expectancy ≥12 weeks, measurable advanced/metastatic solid tumors, and adequate organ function. Exclusions include prior ADC/hypersensitivity, unresolved toxicities (>G1), active CNS metastases, NYHA II-IV cardiac disease, HBV/HCV/HIV positivity, or conditions hindering compliance. Contraception is mandatory for 6 months post-treatment.    Click to Show/Hide
Administration Dosage	SHR-A1403 is a humanized anti C-Met immunoglobulin G2 (IgG2) monoclonal antibody conjugated with microtubule inhibitor. SHR-A1403 is provided as the lyophilized powder,40 mg/vial.SHR-A1403 was given intravenously per 3 weeks at the day 1.Intravenous infusion over 30 min
Related Clinical Trial
NCT Number	NCT03856541	Clinical Status	PHASE1
Clinical Description	A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR-A1403 With Intravenous Infusion in Patients With Advanced Solid Tumors
Primary Endpoint	The study assesses treatment-related AEs of SHR-A1403 in advanced solid tumor patients over 24 months, evaluating incidence, severity (NCI CTCAE), and DLTs during cycle 1, with MTD determined as the highest dose below/close to 30% toxicity probability.
Other Endpoint	Pharmacokinetic analysis includes Tmax, Cmax, T1/2, CL/F, Vd/F, AUC, Rac, and ADA assessment over 24 months. Efficacy is measured via RECIST v1.1, with C-Met expression explored in blood/tissue. RP2D will be determined based on safety using CTCAE v4.03 criteria.
Experiment 2 Reporting the Activity Date of This ADC					[5]
Related Clinical Trial
NCT Number	NCT03856541	Clinical Status	Phase 1
Clinical Description	A phase 1, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of SHR-a1403 with intravenous infusion in patients with advanced solid tumors.

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.50%	High MET expression (MET+++)
Method Description	HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (1 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model	Hepatic cancer PDX model (PDX: HCC)
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.30%	High MET expression (MET+++)
Method Description	HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (3 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model	Hepatic cancer PDX model (PDX: HCC)
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50%	High MET expression (MET+++)
Method Description	HCC tumor cells derived from patients (passage 5) were implanted subcutaneously in BALB/c nude mice at an initial tumor size of approximately 30 mm3. In this model,tumor-bearing mice were given vehicle,SHR-A1403 (10 mg/kg),or SHR-A1403 mAb (10 mg/kg) via twice-weekly intravenous injection for two consecutive weeks.
In Vivo Model	Hepatic cancer PDX model (PDX: HCC)

Experiment 1 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0%	Negative MET expression (MET-)
Method Description	Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.    Click to Show/Hide
In Vivo Model	Non-small cell lung cancer HCC827 CDX model (CDX: HA1; Afatinib resistant)
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Afatinib resistant; HA1)		CVCL_2063
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 34.50%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.    Click to Show/Hide
In Vivo Model	Hepatic cancer CDX model
In Vitro Model	Adult hepatocellular carcinoma	HCCLM3 cells		CVCL_6832
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 41.80%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.    Click to Show/Hide
In Vivo Model	Lung cancer CDX model
In Vitro Model	Lung cancer	Lung cancer cells		Homo sapiens
Experiment 4 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 42.80%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 1 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric cancer	Gastric cancer cells		Homo sapiens
Experiment 5 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 59.30%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.    Click to Show/Hide
In Vivo Model	Lung cancer CDX model
In Vitro Model	Lung cancer	Lung cancer cells		Homo sapiens
Experiment 6 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.30%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.    Click to Show/Hide
In Vivo Model	Hepatic cancer CDX model
In Vitro Model	Adult hepatocellular carcinoma	HCCLM3 cells		CVCL_6832
Experiment 7 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 84.60%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 3 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric adenocarcinoma	MKN45 cells		CVCL_0434
Experiment 8 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.90%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the MKN-45 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric adenocarcinoma	MKN45 cells		CVCL_0434
Experiment 9 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 91.60%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the NCI-H1993 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.    Click to Show/Hide
In Vivo Model	Lung cancer CDX model
In Vitro Model	Lung adenocarcinoma	NCI-H1993 cells		CVCL_1512
Experiment 10 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.80%	High MET expression (MET+++)
Method Description	Effects of SHR-A1403 were further determined in vivo by assessing the growth of HCC827 and HA1 xenograft tumors. Tumor-bearing mice,established by s.c. inoculation of HCC827 and HA1 cells,were randomized into vehicle,AZD9291 (3 mg/kg single dose,i.g.) and SHR-A1403 (10 mg/kg single dose,i.v.) treatment groups when average tumor volumes reached approximately 100-200 mm3.    Click to Show/Hide
In Vivo Model	Non-small cell lung cancer CDX model
In Vitro Model	Lung adenocarcinoma	HCC827 cells		CVCL_2063
Experiment 11 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.80%	High MET expression (MET+++)
Method Description	SHR-A1403 was evaluated in xenograft mice bearing cancer cells with high c-Met expression,including hepatic cancer HCCLM3,lung cancer NCI-H1993,and gastric cancer MKN-45 cells,and the effects were compared with the effects of SHR-A1403 mAb,the free toxin,or their combination. In the HCCLM3 xenograft model,SHR-A1403 was administered at a single dose of 10 mg/kg.    Click to Show/Hide
In Vivo Model	Hepatic cancer CDX model
In Vitro Model	Adult hepatocellular carcinoma	HCCLM3 cells		CVCL_6832

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.2 ng/mL	High MET expression (MET+++; IHC 3+)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Adult hepatocellular carcinoma	HCCLM3 cells		CVCL_6832
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.8 ng/mL	Negative MET expression (MET-)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Gastric adenocarcinoma	MKN45 cells		CVCL_0434
Experiment 3 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.8 ng/mL	Moderate MET expression (MET++)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Afatinib resistant; HA1)		CVCL_2063
Experiment 4 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	16.3 ng/mL	High MET expression (MET+++)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Lung adenocarcinoma	NCI-H1993 cells		CVCL_1512
Experiment 5 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	17.8 ng/mL	High MET expression (MET+++)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Gefitinib resistant)		CVCL_2063
Experiment 6 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	26.6 ng/mL	Negative MET expression (MET-)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Gefitinib resistant)		CVCL_2063
Experiment 7 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	46.7 ng/mL	Moderate MET expression (MET++)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Lung papillary adenocarcinoma	NCI-H441 cells		CVCL_1561
Experiment 8 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	53.9 ng/mL	High MET expression (MET+++; IHC 3+)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Invasive breast carcinoma	Hs 578T cells		CVCL_0332
Experiment 9 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	78.2 ng/mL	High MET expression (MET+++)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Prostate carcinoma	PC-3 cells		CVCL_0035
Experiment 10 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	99.4 ng/mL	Moderate MET expression (MET++)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Gefitinib resistant)		CVCL_2063
Experiment 11 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	130.8 ng/mL	High MET expression (MET+++)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Gefitinib resistant)		CVCL_2063
Experiment 12 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	214.8 ng/mL	Moderate MET expression (MET++)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Clear cell renal cell carcinoma	Caki-1 cells		CVCL_0234
Experiment 13 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	918.9 ng/mL	Moderate MET expression (MET++)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells		CVCL_2063
Experiment 14 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1987.5 ng/mL	High MET expression (MET+++; IHC 3+)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Lung adenocarcinoma	A-549 cells		CVCL_0023
Experiment 15 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10 ug/mL	High MET expression (MET+++)
Method Description	The effects of SHR-A1403 on the proliferation of various types of human cancer cells were evaluated and compared with the effects of SHR-A1403 mAb and the free toxin SHR152852.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 16 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 30 ug/mL	Negative MET expression (MET-)
Method Description	To establish the EGFR inhibitor-resistant NSCLC cells,HCC827 cells were grown initially in medium containing 10 nmol/L gefitinib or afatinib. To exam the ability of the ADC,SHR-A1403,to overcome AZD9291 resistance. Human tumor xenografts were established by s.c. inoculation of nude mice with HCC827,HA1 or HG3 cells. Tumor-bearing mice were randomized into groups and treated with vehicle,AZD9291 intragastric administration (i.g.) or SHR-A1403 intravenous injection (i.v.) when average tumor volume reached approximately 100-200 mm3. Resistance ratio = IC50 (resistant cells)/IC50 (HCC827).    Click to Show/Hide
In Vitro Model	Lung adenocarcinoma	HCC827 cells (Afatinib resistant; HA2)		CVCL_2063

Ref 1	SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models
Ref 2	Preclinical pharmacokinetics of a novel anti-c-Met antibody-drug conjugate, SHR-A1403, in rodents and non-human primates
Ref 3	A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients with Small Cell Lung Cancer
Ref 4	A Study of SHR-A1403 in Patients With Advanced Solid Tumor
Ref 5	A Phase I, Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR-A1403 With Intravenous Infusion in Patients With Advanced Solid Tumors
Ref 6	SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models. Acta Pharmacol Sin. 2019 Jul;40(7):971-979.
Ref 7	SHR-A1403, a novel c-mesenchymal-epithelial transition factor (c-Met) antibody-drug conjugate, overcomes AZD9291 resistance in non-small cell lung cancer cells overexpressing c-Met. Cancer Sci. 2019 Nov;110(11):3584-3594.