Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0QZHYU
|
|||||
|---|---|---|---|---|---|---|
| ADC Name |
Sirtratumab vedotin
|
|||||
| Synonyms |
sirtratumab vedotin; ASG-15ME; AGS-15E
Click to Show/Hide
|
|||||
| Organization |
Seagen (Top20 MNC) (Originator);Agensys (Top20 MNC)
|
|||||
| Drug Status |
Phase 1 (discontinued)
|
|||||
| Drug-to-Antibody Ratio |
4
|
|||||
| Structure |
|
|||||
|
|
||||||
| Antibody Name |
Sirtratumab
|
Antibody Info | ||||
| Antigen Name |
SLIT and NTRK-like protein 6 (SLITRK6)
|
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
|
|||||
The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||
|---|---|---|---|---|---|---|---|---|---|
| Urothelial cancer |
1 Trials
|
General Information of The ADMET Data Related to This ADC(2027 Update)
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Elimination Half-Life (t1/2) | 2.3 | day |
Serum concentrations of ASG-15ME decreased multi-exponentially and exposure was dose-proportional. ASG-15ME half-life is 2.3 days
|
[1] |
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Patient-derived Xenograft Model
Discovered Using Cell Line-derived Xenograft Model
| 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
|
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) | 13.00, 29.00, 40.00, 40.00 % | 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 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Progression Free Survival |
16 weeks
|
|||
| Patients Enrolled |
Eligible patients must have histologically confirmed TCCU with specific prior treatment requirements per cohort (Parts A, B, C). Key inclusion criteria include measurable disease, ECOG status 0-2, life expectancy ≥3 months, and adequate organ function. Exclusion criteria cover severe neuropathy, uncontrolled CNS metastases, recent investigational/cancer therapy, significant cardiac disease, active infections, major surgery within 28 days, and specific ocular conditions.
Click to Show/Hide
|
||||
| Administration Dosage |
ASG-15ME was administered IV weekly for 3 out of every 4 wks until no further benefit. 6 dose levels were studied: 0.1, .25, .5, 0.75, 1, or 1.25 mg/kg.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT01963052 | Clinical Status | PHASE1 | ||
| 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 | ||||
| Primary Endpoint |
The primary safety endpoint is the incidence of adverse events over 36 months, while pharmacokinetic parameters for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) including CEOI, Cmax, Ctrough, Tmax, AUC0-7, t1/2, CL, and Vss are assessed during specific dosing cycles up to 6 months.
|
||||
| Other Endpoint |
Secondary endpoints include Anti-Drug Antibody (ADA) incidence and tumor response (CR/PR per RECIST 1.1 confirmed ≥28 days), objective response rate, disease control rate (CR/PR/SD), progression-free survival (time from first infusion to progression/death), and duration of response (time from first CR/PR to progression/death) evaluated over 26-36 months.
Click to Show/Hide
|
||||
| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
30%
|
|||
| Patients Enrolled |
Eligible patients must have histologically confirmed TCCU with specific prior treatment requirements per cohort (Parts A, B, C). Key inclusion criteria include measurable disease, ECOG status 0-2, life expectancy ≥3 months, and adequate organ function. Exclusion criteria cover severe neuropathy, uncontrolled CNS metastases, recent investigational/cancer therapy, significant cardiac disease, active infections, major surgery within 28 days, and specific ocular conditions.
Click to Show/Hide
|
||||
| Administration Dosage |
ASG-15ME was administered IV weekly for 3 out of every 4 wks until no further benefit. 6 dose levels were studied: 0.1, .25, .5, 0.75, 1, or 1.25 mg/kg.
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT01963052 | Clinical Status | PHASE1 | ||
| 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 | ||||
| Primary Endpoint |
The primary safety endpoint is the incidence of adverse events over 36 months, while pharmacokinetic parameters for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) including CEOI, Cmax, Ctrough, Tmax, AUC0-7, t1/2, CL, and Vss are assessed during specific dosing cycles up to 6 months.
|
||||
| Other Endpoint |
Secondary endpoints include Anti-Drug Antibody (ADA) incidence and tumor response (CR/PR per RECIST 1.1 confirmed ≥28 days), objective response rate, disease control rate (CR/PR/SD), progression-free survival (time from first infusion to progression/death), and duration of response (time from first CR/PR to progression/death) evaluated over 26-36 months.
Click to Show/Hide
|
||||
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 73.40% | 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 | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 86.90% | 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 | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 88.40% | 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) | ||||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 88.90% | 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 | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 91.10% | 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 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| 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 | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 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 | ||
References