ADC ID	DRG0QZHYU
ADC Name	Sirtratumab vedotin
Synonyms	AGS-15E; AGS15CSGD-1006; ASG 15E; ASG 15ME; ASG-15ME; Ha15-10ac.1vcMMAE; Ha15-10ac12vcMMAE; sirtratumab vedotin    Click to Show/Hide
Organization	Agensys, Inc.; Astellas Pharma Global Development, Inc.; Seagen Inc.
Drug Status	Phase 1
Indication	In total 2 Indication(s) Bladder cancer [ICD11:2C94] Phase 1 Urothelial cancer [ICD11:2C9Z] Phase 1
Drug-to-Antibody Ratio	4
Structure
	3D MOL			2D MOL
Antibody Name	Sirtratumab					Antibody Info
Antigen Name	SLIT and NTRK-like protein 6 (SLITRK6)					Antigen Info
Payload Name	Monomethyl auristatin E					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	Mc-Val-Cit-PABC					Linker Info
Conjugate Type	Random conjugation through reduced inter-chain cysteines.
Combination Type	Vedotin
Puchem SID	472419166 , 381128083

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT01963052	Phase 1	A phase 1 study of the safety and pharmacokinetics of escalating doses of AGS15E given as monotherapy in subjects with metastatic urothelial cancer.

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 73.4	%	Bladder cancer PDX model (PDX: AG-B8)
Tumor Growth Inhibition value (TGI)	≈ 86.9	%	Bladder cancer PDX model (PDX: AG-B7)
Tumor Growth Inhibition value (TGI)	≈ 88.4	%	Bladder cancer PDX model (PDX: AG-B8)

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 88.9	%	RT-4 cells	Bladder carcinoma
Tumor Growth Inhibition value (TGI)	≈ 91.1	%	NCI-322M cells	Lung cancer

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.99	nM	CHP-212 cells	Neuroblastoma
Half Maximal Inhibitory Concentration (IC50)	> 10	uM	IGROV-1 cells	Ovarian endometrioid adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Objective Response Rate (ORR)	13.00% (0.50 mg/kg), 29.00% (0.75 mg/kg), 40.00% (1.00 mg/kg), 40.00% (1.25 mg/kg)	High SLITRK6 expression (SLITRK6+++; IHC H-score=230)
Patients Enrolled	Metastatic uroepithelial carcinoma (mUC) patients unselected for SLITRK6 expression (determined by an IHC assay) and previously treated with 1 prior chemo regimen or unfit for cisplatin.
Administration Dosage	Administered IV weekly for 3 out of every 4 weeks.
Related Clinical Trial
NCT Number	NCT01963052	Clinical Status	Phase 1
Clinical Description	A phase 1 study of the safety and pharmacokinetics of escalating doses of AGS15E given as monotherapy in subjects with metastatic urothelial cancer.

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 73.40% (Day 17)	Moderate SLITRK6 expression (SLITRK6++; IHC H-score=185)
Method Description	PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.25 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model	Bladder cancer PDX model (PDX: AG-B8)
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 86.90% (Day 25)	High SLITRK6 expression (SLITRK6+++; IHC H-score=280)
Method Description	PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.5 mg/kg,2x per week i.v in AG-B7 PDX model. The last dose was given on day 21.
In Vivo Model	Bladder cancer PDX model (PDX: AG-B7)
Experiment 3 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.40% (Day 17)	High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description	PDX models were established by subcutaneous implantation of xenograft fragments (AG-B7 or AG-B8) in the flanks of SCID mice. When the tumor volume reached approximately 200 mm3,Sirtratumab Vedotin was dosed at 0.5 mg/kg,2x per week i.v in AG-B8 PDX model. The last dose was given on day 14.
In Vivo Model	Bladder cancer PDX model (PDX: AG-B8)

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.90% (Day 30)	High SLITRK6 expression (SLITRK6+++)
Method Description	CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. When the tumor volume reached approximately 230 mm3, a single dose of Sirtratumab Vedotin, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model	Bladder cancer CDX model
In Vitro Model	Bladder carcinoma	RT-4 cells		CVCL_0036
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 91.10% (Day 21)	Negative SLITRK6 expression (SLITRK6-)
Method Description	CDX models were established by subcutaneous injection of between 2 and 10 million SW780, RT4 (ATCC) or NCI-H322M (NCI) cells in SCID mice. Sirtratumab Vedotin was administered twice weekly at 3 mg/kg (n = 6) starting when the tumor volume reached approximately 200 mm3.
In Vivo Model	Lung cancer NCI-322M CDX model
In Vitro Model	Lung cancer	NCI-322M cells		Homo sapiens

Experiment 1 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.99 nM
Method Description	ASG-15ME was tested for its ability to kill several SLITRK6-positive cell lines in vitro. The viability of CHP-212 cells treated with ASG-15ME was compared with that of target negative cells (IGR-OV1) or cells treated with an isotype control antibody to determine IC50 values.
In Vitro Model	Neuroblastoma	CHP-212 cells		CVCL_1125
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10.00 uM	High SLITRK6 expression (SLITRK6+++; IHC H-score=250)
Method Description	ASG-15ME was tested for its ability to kill several SLITRK6-positive cell lines in vitro. The viability of CHP-212 cells treated with ASG-15ME was compared with that of target negative cells (IGR-OV1) or cells treated with an isotype control antibody to determine IC50 values.
In Vitro Model	Ovarian endometrioid adenocarcinoma	IGROV-1 cells		CVCL_1304

Ref 1	Phase 1 study of SGN-B7H4V, a novel, investigational vedotin antibodydrug conjugate directed to B7-H4, in patients with advanced solid tumors (SGNB7H4V-001, trial in progress). J Clin Oncol. 2022 40:16_suppl, TPS3155-TPS3155.
Ref 2	Development of ASG-15ME, a Novel Antibody-Drug Conjugate Targeting SLITRK6, a New Urothelial Cancer Biomarker. Mol Cancer Ther. 2016 Jun;15(6):1301-10.