Antibody Information
General Information of This Antibody
| Antibody ID | ANI0FQFZL |
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| Antibody Name | Sirtratumab |
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| Organization | Agensys, Inc. |
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| Indication | Solid tumors |
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| Synonyms |
AGS-15C; AGS15C; Ha15-10ac12; Ha15-10ac12.1
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| Antibody Type | Monoclonal antibody (mAb) |
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| Antibody Subtype | Humanized IgG2-kappa |
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| Antigen Name | SLIT and NTRK-like protein 6 (SLITRK6) |
Antigen Info | ||||
| Click to Show/Hide the Sequence Information of This Antibody | ||||||
| Heavy Chain Sequence |
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNQYY
ADSVKGRFTISRDNSKNTLFLQMHSLRAEDTAVYYCARGLTSGRYGMDVWGQGTTVTVSS ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFR VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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| Heavy Chain Varible Domain |
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNQYY
ADSVKGRFTISRDNSKNTLFLQMHSLRAEDTAVYYCARGLTSGRYGMDVWGQGTTVTVSS Click to Show/Hide
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| Heavy Chain Constant Domain 1 |
ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV Click to Show/Hide
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| Heavy Chain Constant Domain 2 |
APPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKP
REEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTK Click to Show/Hide
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| Heavy Chain Constant Domain 3 |
GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDS
DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
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| Heavy Chain Hinge Region |
ERKCCVECPPCP
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| Heavy Chain CDR 1 |
GFTFSSYG
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| Heavy Chain CDR 2 |
IWYDGSNQ
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| Heavy Chain CDR 3 |
ARGLTSGRYGMDV
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| Light Chain Sequence |
DIVMTQSPLSLPVTPGEPASISCRSSQSLLLSHGFNYLDWYLQKPGQSPQLLIYLGSSRA
SGVPDRFSGSGSGTDFTLKISRVEAEDVGLYYCMQPLQIPWTFGQGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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| Light Chain Varible Domain |
DIVMTQSPLSLPVTPGEPASISCRSSQSLLLSHGFNYLDWYLQKPGQSPQLLIYLGSSRA
SGVPDRFSGSGSGTDFTLKISRVEAEDVGLYYCMQPLQIPWTFGQGTKVEIK Click to Show/Hide
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| Light Chain Constant Domain |
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD
SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
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| Light Chain CDR 1 |
QSLLLSHGFNY
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| Light Chain CDR 2 |
LGS
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| Light Chain CDR 3 |
MQPLQIPWT
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The Activity Data of This Antibody
| Antibody Activity Information 1 | [1] | |||||
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Dissociation Constant (Kd)
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15
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pM
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SW780 cells | CVCL_1728 | ||
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| Antigen Expression | Positive SLITRK6 expression (SLITRK6+++/++) | |||||
| Antibody Function | Confirm the effect of the drug conjugation with the anti-SLITRK6 mAb and ADC on binding activity to cell line. | |||||
| Antibody Antigen Binding Assay | FACS analysis to determine maximum binding (Bmax) and affinity of ASG-15ME (ADC) and AGS-15C (unconjugated mAb). For the assay, antibodies were serially diluted and incubated with SW-780 cells (50,000 cells/well) at a final concentration of 40.0 to 0.00067 nmol/L and added to the SW-780 cells for overnight incubation at 4C. | |||||
Each Antibody-drug Conjugate Related to This Antibody
Full Information of The Activity Data of The ADC(s) Related to This Antibody
Sirtratumab vedotin [Phase 1 (discontinued)]
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.
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| Administration Dosage |
Administered IV weekly for 3 out of every 4 weeks.
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| 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.
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| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Progression Free Survival |
16 weeks
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| 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.
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| 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.
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| 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
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| 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.
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| 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.
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| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
30%
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| 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.
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| 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.
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| 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
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| 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.
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| 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.
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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.
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| 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.
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| 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.
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| 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.
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| 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.
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| 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
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| 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.
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| 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.
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| In Vitro Model | Ovarian endometrioid adenocarcinoma | IGROV-1 cells | CVCL_1304 | ||
ASG-15MF [Investigative]
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 62.90% | 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,ASG-15MF 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.
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| 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) | ≈ 63.40% | High SLITRK6 expression (SLITRK6+++; IHC H-score=230) | ||
| 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,ASG-15MF 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.
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| 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) | ≈ 80% | 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,ASG-15MF 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.
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| 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) | ≈ 35.20% | Moderate SLITRK6 expression (SLITRK6++; IHC H-score=185) | ||
| 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. ASG-15MF was administered twice weekly at 3 mg/kg (n = 6) starting when the tumor volume reached approximately 200 mm3.
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| In Vivo Model | NCI-322M CDX model | ||||
| In Vitro Model | Lung cancer | NCI-322M cells | Homo sapiens | ||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 81.30% | High SLITRK6 expression (SLITRK6+++; IHC H-score=280) | ||
| 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 ASG-15MF, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
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| In Vivo Model | Bladder cancer CDX model | ||||
| In Vitro Model | Bladder cancer | Bladder cancer cells | Homo sapiens | ||
References