General Information of This Linker
Linker ID
LIN0TAFAV
Linker Name
Maleimido-caproyl
Linker Type
Flexible reactive (thiol) linker
Antibody-Linker Relation
Uncleavable
Structure
Formula
C10H13NO4
Isosmiles
O=C(O)CCCCCN1C(=O)C=CC1=O
InChI
InChI=1S/C10H13NO4/c12-8-5-6-9(13)11(8)7-3-1-2-4-10(14)15/h5-6H,1-4,7H2,(H,14,15)
InChIKey
WOJKKJKETHYEAC-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
211.217
Polar area
74.68
Complexity
15
xlogp Value
0.5564
Heavy Count
15
Rot Bonds
6
Hbond acc
3
Hbond Donor
1
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Belantamab mafodotin [Approved]
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Objective Response Rate (ORR)
60.00%
Patients Enrolled
Histologically or cytologically confirmed MM, a European Cooperative Oncology Group performance status of 0 or 1, prior therapy with alkylators, PI and IMiD, had undergone stem cell transplant (if eligible) and refractory to the last line of treatment (defined as progressive disease on or within 60 days of completion of the last therapy) that included stem cell transplant and those patients with a history of autologous stem cell transplant must have received the transplant >100 days prior to study enrolment and have no active infection.

   Click to Show/Hide
Administration Dosage
Doses ranging between 0.03 mg/kg and 4.60 mg/kg was administered as a 1-hour intravenous infusion every 3 weeks for a maximum of 16 cycles.
Related Clinical Trial
NCT Number NCT02064387  Clinical Status Phase 1
Clinical Description
A phase 1 open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of the antibody drug conjugate GSK2857916 in subjects with relapsed/refractory multiple myeloma and other advanced hematologic malignancies expressing BCMA.
Primary Endpoint
The primary endpoints of the trial were to determine the safety, tolerability, maximum tolerated dose (MTD) and RP2D and schedule of GSK2857916. Median PFS (post hoc analysis) was 7.90 months (95% CI: 3.1-not estimable),Overall response rate at 3.40 mg/kg in Part 2 was 60.00% (21/35; 95% confidence interval: 42.10%-76.10%).
Other Endpoint
PK profile (single dose area under the curve, maximum serum concentration [Cmax], time to Cmax , clearance, steady-state volume of distribution [Vss], half-life [t]; repeat dose Cmax and trough plasma concentration), the incidence of anti-drug antibodies, and clinical activity measured as overall response rate (ORR), defined as the percentage of subjects achieving confirmed partial response or better (PR) and clinical benefit rate, defined as the percentages of subjects with minimal response or better (MR).

   Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
60.00%
High BCMA expression (BCMA +++)
Patients Enrolled
Eligible adult (18 years of age) patients for part 2 had histologically or cytologically confirmed MM, Eastern Cooperative Oncology Group performance status 0 or 1, prior therapy with alkylators, proteasome inhibitors and immunomodulators, and were refractory to the last line of treatment.
Administration Dosage
GSK2857916 3.4 mg/kg was administered through 1-h intravenous infusions once every 3 weeks, for a maximum of 16 cycles.
Related Clinical Trial
NCT Number NCT02064387   Clinical Status Phase 1
Clinical Description
A Phase I open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of the antibody drug conjugate GSK2857916 in subjects with relapsed/refractory multiple myeloma and other advanced hematologic malignancies expressing BCMA.
Primary Endpoint
Objective response rate=60.00% (95% CI 42.10-76.10), comprising 5 (14.29%) achieving complete responses and 16 (45.71%) achieving partial responses.
Other Endpoint
The median progression-free survival was 12.00 months and the median duration of response was 14.30 months.
Experiment 3 Reporting the Activity Date of This ADC [3]
Related Clinical Trial
NCT Number NCT03769506  Clinical Status Phase 3
Clinical Description
A phase 3, randomized, double-arm, open-label, controlled trial of ASP-1929 photoimmunotherapy versus physician's choice standard of care for the treatment of locoregional, recurrent head and neck squamous cell carcinoma in patients who have failed or progressed on or after at least two lines of therapy, of which at least one line must be systemic therapy.

   Click to Show/Hide
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Efficacy Data Half Maximal Effective Concentration (EC50)
30.60 ug/mL
Moderate BCMA expression (BCMA++)
Method Description
Cells (5 x 105 cells/mL) were left untreated or exposed to the indicated treatments for the indicated time. Cells were counted on a Vi-Cell-XR Cell Viability Analyzer (Beckman Coulter).
In Vitro Model Thymoma EL4 cells (BCMA expression) CVCL_0255
Depatuxizumab mafodotin [Phase 3]
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [5]
Efficacy Data Median progression-free survival (mPFS)
8.00 (depatux-m group); 6.30 (placebo group)
High EGFR expression (EGFR +++)
Patients Enrolled
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage
Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/28, 19,21 and allowed to continue until disease progression.
Experiment 2 Reporting the Activity Date of This ADC [5]
Efficacy Data Median Overall Survival (mOS)
18.90 (depatux-m group); 18.70(placebo group)
High EGFR expression (EGFR +++)
Patients Enrolled
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage
Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/2819, 21 and allowed to continue until disease progression.
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.50% (Day 40) Positive EGFR expression (EGFR+++/++)
Method Description
To establish xenografts, 2 x 106 MSTO-211H cells mixed with 75-uL Matrigel were injected subcutaneously in the right flank of 5 to 6-week-old female BALB/c nu/nu miceFor the MSTO-211H study, mice received either ABT-414, ABBV-221 or ADC control (3 mg/kg) every 4 days.
In Vivo Model MSTO-211H CDX model
In Vitro Model Pleural biphasic mesothelioma MSTO-211H cells CVCL_1430
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.00 ug/mL - 35.00 ug/mL
Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural biphasic mesothelioma MSTO-211H cells CVCL_1430
Experiment 3 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.00 ug/mL - 35.00 ug/mL
Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H28 cells CVCL_1555
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.00 ug/mL - 35.00 ug/mL
Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H2052 cells CVCL_1518
Experiment 5 Reporting the Activity Date of This ADC [6]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.00 ug/mL - 35.00 ug/mL
Positive EGFR expression (EGFR+++/++)
Method Description
Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model Pleural mesothelioma NCI-H2052 cells CVCL_1518
Lonigutamab ugodotin [Phase 2]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Related Clinical Trial
NCT Number NCT03316638  Clinical Status Phase 1/2
Clinical Description
Phase 1/2 open label dose escalation and dose expansion study of intravenous infusion of W0101, an antibody-drug conjugate, in patients with advanced or metastatic solid tumors. International, multicenter, open label study.
Revealed Based on the Cell Line Data
Click To Hide/Show 8 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% Low IGF1 expression (IGF1+)
Method Description
For the lung cancer models, 7-week-old female athymic nude mice (Envigo) were engrafted subcutaneously with 7 x106 SBC5 cells and treated with W0101 or isotype control ADC at 3 mg/kg every 4 days for 4 cycles.
In Vitro Model Lung small cell carcinoma SBC-5 cells CVCL_1679
Experiment 2 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.00% Moderate IGF1 expression (IGF1++)
Method Description
For the lung cancer models, 7-week-old female athymic nude mice (Envigo) were engrafted subcutaneously with 7 x106 NCI-H2122 cells and treated with W0101 or isotype control ADC at 3 mg/kg every 4 days for 4 cycles.
In Vitro Model Lung adenocarcinoma NCI-H2122 cells CVCL_1531
Experiment 3 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% High IGF1 expression (IGF1+++)
Method Description
For the breast cancer model, 7-week-old female Swiss nude mice (Charles River Laboratories) were engrafted subcutaneously with 5 x106 MCF-7 cells 1 day after subcutaneous implantation of 0.72 mg 17-estradiol 60-day releasing pellets (Innovative Research of America) and treated with W0101 or isotype control ADC at 3 mg/kg every 4 days for 4 cycles.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
Experiment 4 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% Moderate IGF1 expression (IGF1++)
Method Description
For the ovarian cancer model, 7-week-old female SCID mice (Charles River Laboratories) were engrafted subcutaneously with 10 x106 CaoV3 cells and treated with W0101 or isotype control ADC at 3 mg/kg every 4 days for 4 cycles.
In Vitro Model Lung adenocarcinoma NCI-H2122 cells CVCL_1531
Experiment 5 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.01 nM
High IGF1 expression (IGF1+++)
Method Description
Tumor and normal cells were plated in 96-well flat bottomed microplates (100 L/well) in cell culture medium and incubated overnight at 37°C in 5% CO2. The next day, increasing concentrations of W0101 or isotype control ADC (010 ug/mL) were added into 3 replicate wells containing cells (10 L/well). Plates were incubated for 6 days at 37°C in 5% CO2. Cell viability was determined by measuring ATP using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). Luminescence was read using a Multimode Microplate Reader (Mithras LB940, Berthold Technologies). The percentage cell viability was calculated for each concentration considering 0 ug/mL ADC as 100% viability. The IC50 was calculated using Prism software. Three independent experiments were performed.

   Click to Show/Hide
In Vitro Model Invasive breast carcinoma MCF-7 cells CVCL_0031
Experiment 6 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.63 nM
Moderate IGF1 expression (IGF1++)
Method Description
Tumor and normal cells were plated in 96-well flat bottomed microplates (100 L/well) in cell culture medium and incubated overnight at 37°C in 5% CO2. The next day, increasing concentrations of W0101 or isotype control ADC (010 ug/mL) were added into 3 replicate wells containing cells (10 L/well). Plates were incubated for 6 days at 37°C in 5% CO2. Cell viability was determined by measuring ATP using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). Luminescence was read using a Multimode Microplate Reader (Mithras LB940, Berthold Technologies). The percentage cell viability was calculated for each concentration considering 0 ug/mL ADC as 100% viability. The IC50 was calculated using Prism software. Three independent experiments were performed.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma NCI-H2122 cells CVCL_1531
Experiment 7 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 nM Moderate IGF1 expression (IGF1++)
Method Description
Tumor and normal cells were plated in 96-well flat bottomed microplates (100 L/well) in cell culture medium and incubated overnight at 37°C in 5% CO2. The next day, increasing concentrations of W0101 or isotype control ADC (010 ug/mL) were added into 3 replicate wells containing cells (10 L/well). Plates were incubated for 6 days at 37°C in 5% CO2. Cell viability was determined by measuring ATP using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). Luminescence was read using a Multimode Microplate Reader (Mithras LB940, Berthold Technologies). The percentage cell viability was calculated for each concentration considering 0 ug/mL ADC as 100% viability. The IC50 was calculated using Prism software. Three independent experiments were performed.

   Click to Show/Hide
In Vitro Model Ovarian serous adenocarcinoma Caov-3 cells CVCL_0201
Experiment 8 Reporting the Activity Date of This ADC [8]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100.00 nM Low IGF1 expression (IGF1+)
Method Description
Tumor and normal cells were plated in 96-well flat bottomed microplates (100 L/well) in cell culture medium and incubated overnight at 37°C in 5% CO2. The next day, increasing concentrations of W0101 or isotype control ADC (010 ug/mL) were added into 3 replicate wells containing cells (10 L/well). Plates were incubated for 6 days at 37°C in 5% CO2. Cell viability was determined by measuring ATP using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). Luminescence was read using a Multimode Microplate Reader (Mithras LB940, Berthold Technologies). The percentage cell viability was calculated for each concentration considering 0 ug/mL ADC as 100% viability. The IC50 was calculated using Prism software. Three independent experiments were performed.

   Click to Show/Hide
In Vitro Model Lung small cell carcinoma SBC-5 cells CVCL_1679
TAK-500 [Phase 1]
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Related Clinical Trial
NCT Number NCT04879849  Clinical Status Phase 1
Clinical Description
An open-label, phase 1, dose-escalation study to evaluate the safety and preliminary antitumor activity of TAK-676 with pembrolizumab following radiation therapy in the treatment of non-small-cell lung cancer, triple-negative breast cancer, or squamous-cell carcinoma of the head and neck that has progressed on checkpoint inhibitors.
Experiment 2 Reporting the Activity Date of This ADC [10]
Related Clinical Trial
NCT Number NCT04420884  Clinical Status Phase 1
Clinical Description
An open-label, dose escalation, phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-676 as a single agent and in combination with pembrolizumab in adult patients with advanced or metastatic solid tumors.
SNS-622-DM1 [Investigative]
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [11]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 36.75% (Day 56) Positive ASPH expression (ASPH +++/++)
Method Description
Mice bearing an approximately 100 mm3 tumor xenograft were intravenously injected weekly with 2.5 mg/kg of SNS-622 or SNS-622-DM1, and tumor growth was monitored.
In Vivo Model Pancreatic ductal adenocarcinoma PDX model
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [11]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 55.56% (Day 22) Positive ASPH expression (ASPH +++/++)
Method Description
MIA PaCa2-empty vector and MIA-PaCa2-ASPH cell lines generated sc tumors in the NSG mice were treated with SNS-622-DM1 (5 mg/kg. every 7 day) and a non-relevant IgG mAb also conjugated with DM1.
In Vivo Model MIA PaCa2 CDX model
In Vitro Model Pancreatic ductal adenocarcinoma MIA PaCa-2 cells CVCL_0428
ASG-15MF [Investigative]
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 62.90% (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,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.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Experiment 2 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 63.40% (Day 25) 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.
In Vivo Model Bladder cancer PDX model (PDX: AG-B7)
Experiment 3 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.00% (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,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.
In Vivo Model Bladder cancer PDX model (PDX: AG-B8)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 35.20% (Day 21) 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.
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 [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.30% (Day 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.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder cancer Bladder cancer cells Homo sapiens
HuM25-mcMMAF-E2 [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI)
0.00%
Positive LRRC15 expression (LRRC15 +++/++)
Method Description
LRRC15 expression on stromal cells asassessed by IHC in an untreated xenograft tumor of 200-800 mm in volume, representative for eachxenograft model. In vivo activity of huM25-MCMMAF-E2 (12 mg/kg) was demonstrated in PANC-1 xenografts.
In Vivo Model PANC-1 CDX model
In Vitro Model Pancreatic ductal adenocarcinoma PANC-1 cells CVCL_0480
Experiment 2 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI)
8.47% (Day 11)
High LRRC15 expression (LRRC15+++; IHC 3+)
Method Description
LRRC15 expression on stromal cells asassessed by IHC in an untreated xenograft tumor of 200-800 mm in volume, representative for eachxenograft model. In vivo activity of huM25-MCMMAF-E2 (6 mg/kg) was demonstrated in EBC-1 xenografts.
In Vivo Model EBC-1 CDX model
In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.01 nM - 0.10 nM
Positive LRRC15 expression (LRRC15 +++/++)
Method Description
Cancer cell lines were incubated with compounds for 72 h. IC50 values were determined by quantitating viable cells using a CellTiter-Glo luminescent assay.
In Vitro Model Colon carcinoma HCT 116 cells CVCL_0291
Anti-BCMA J6M0-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 24.38% (Day 21) High BCMA expression (BCMA+++)
Method Description
Mice were treated with either a single intravenous dose of the ADCs at 0.3 mg/kg or dosed intravenously with J6M0-mc-MMAFweekly at a dose of 0.3 mg/kg for 2 weeks.
In Vivo Model NCI-H929 CDX model
In Vitro Model Plasma cell myeloma NCI-H929 cells CVCL_1600
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 65.09% (Day 32) Moderate BCMA expression (BCMA++)
Method Description
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 4 weeks. Control mice were left untreated.
In Vivo Model MM.1S CDX model
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 66.25% (Day 21) Moderate BCMA expression (BCMA++)
Method Description
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 3 weeks. Control mice were left untreated.
In Vivo Model JJN-3 CDX model
In Vitro Model Plasma cell myeloma JJN-3 cells CVCL_2078
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84.86% (Day 35) High BCMA expression (BCMA+++)
Method Description
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 3 mg/kg for 4 weeks. Control mice were left untreated.
In Vivo Model MM.1R CDX model
In Vitro Model Plasma cell myeloma MM1.R cells CVCL_8794
Revealed Based on the Cell Line Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
29.28 nM
Moderate BCMA expression (BCMA++)
Method Description
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 0 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 2 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
55.55 nM
Moderate BCMA expression (BCMA++)
Method Description
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 75 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
159.70 nM
Moderate BCMA expression (BCMA++)
Method Description
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 270 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.46 uM
Moderate BCMA expression (BCMA++)
Method Description
The ability of the ADCs to kill multiple myeloma cells in vitro inthe presence of soluble BCMA (sBCMA, 720 ng/ml) as compared to the 09-SG3249 ADC was evaluated in MM.1S cells, except that tested cell lines also were treated with BCMA-containing conditioned media collected from Ad293 cells expressing human BCMA.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Ab3-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 30.23% (Day 33) Positive EGFR expression (EGFR+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg to thetail of each mouse.
In Vivo Model EBC-1 CDX model
In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
HA15-1C25F [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 35.90% (Day 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 Ha15-1c25F, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder cancer Bladder cancer cells Homo sapiens
HA15-1ABE16F [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 44.70% (Day 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 Ha15-1abe16F, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder cancer Bladder cancer cells Homo sapiens
RBGO1-mcF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [16]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 60.00% (Day 20) Positive RAGE expression (RAGE+++/++)
Method Description
Nude athymic mice were divided into three treatment groups of six mice each. Mice were treated with PBS (control) or RBGO1 ADC at either 3 mg/kg or 20mg/kg N intravenous injection. Bodyweight was measured at days 3, 6, 8, 13, 17 and 21 and mouse health assessed daily.
In Vivo Model HEC-1-A CDX model
In Vitro Model Endometrial adenocarcinoma HEC-1-A cells CVCL_0293
HA15-10AC14F [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 64.30% (Day 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 Ha15-10ac14F, 5 mg/kg intravenously, was administered intravenously (iv) to the mice.
In Vivo Model Bladder cancer CDX model
In Vitro Model Bladder cancer Bladder cancer cells Homo sapiens
h1F6-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.44% (Day 18) Positive CD19 expression (CD19+++/++)
Method Description
To establish DOHH1 tumors, 5 x 106 cells were implanted into the right flank of athymic nu/nu female donor mice (Harlan,Indianapolis, IN). When tumors reached ~100 mm3 mice were randomly allocated to treatment groups. The dose of ADC was 4 mg/kg single.
In Vivo Model DOHH1 CDX model
In Vitro Model Diffuse large B-cell lymphoma germinal center B-cell type DoHH2 cells CVCL_1179
Experiment 2 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.21% (Day 25) Positive CD70 expression (CD70+++/++)
Method Description
To establish 786-O tumors, 5 x 106 cells were implanted into the right flank of athymic nu/nu female donor mice. When tumors reached ~100 mm3 mice were randomly allocated to treatment groups. The dose of ADC was 0.5 mg/kg single.
In Vivo Model 786-O CDX model
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
12.00 ng/mL
Positive CD70 expression (CD70+++/++)
Method Description
Log phase cultures of cells were collected and cells plated at seeding densities ranging from 500 - 10,000 cells/well according to pre-determined conditions.After incubating 24 hours to allow surface protein reconstitution, serial dilutions of test conjugates were added and cultures incubated further for 4 days.
In Vitro Model Clear cell renal cell carcinoma Caki-1 cells CVCL_0234
Experiment 2 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
34.00 ng/mL
Positive CD70 expression (CD70+++/++)
Method Description
Log phase cultures of cells were collected and cells plated at seeding densities ranging from 500 - 10,000 cells/well according to pre-determined conditions.After incubating 24 hours to allow surface protein reconstitution, serial dilutions of test conjugates were added and cultures incubated further for 4 days.
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
hBU12-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 76.44% (Day 18) Positive CD19 expression (CD19+++/++)
Method Description
To establish DOHH1 tumors, 5 x 106 cells were implanted into the right flank of athymic nu/nu female donor mice (Harlan,Indianapolis, IN). When tumors reached ~100 mm3 mice were randomly allocated to treatment groups. The dose of ADC was 4 mg/kg single.
In Vivo Model DOHH1 CDX model
In Vitro Model Diffuse large B-cell lymphoma germinal center B-cell type DoHH2 cells CVCL_1179
Experiment 2 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 96.21% (Day 25) Positive CD70 expression (CD70+++/++)
Method Description
To establish 786-O tumors, 5 x 106 cells were implanted into the right flank of athymic nu/nu female donor mice. When tumors reached ~100 mm3 mice were randomly allocated to treatment groups. The dose of ADC was 0.5 mg/kg single.
In Vivo Model 786-O CDX model
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
12.00 ng/mL
Positive CD70 expression (CD70+++/++)
Method Description
Log phase cultures of cells were collected and cells plated at seeding densities ranging from 500 - 10,000 cells/well according to pre-determined conditions.After incubating 24 hours to allow surface protein reconstitution, serial dilutions of test conjugates were added and cultures incubated further for 4 days.
In Vitro Model Clear cell renal cell carcinoma Caki-1 cells CVCL_0234
Experiment 2 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
34.00 ng/mL
Positive CD70 expression (CD70+++/++)
Method Description
Log phase cultures of cells were collected and cells plated at seeding densities ranging from 500 - 10,000 cells/well according to pre-determined conditions.After incubating 24 hours to allow surface protein reconstitution, serial dilutions of test conjugates were added and cultures incubated further for 4 days.
In Vitro Model Renal cell carcinoma 786-O cells CVCL_1051
Ab1-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 81.39% (Day 33) Positive EGFR expression (EGFR+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg to thetail of each mouse.
In Vivo Model EBC-1 CDX model
In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
Experiment 2 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.40% (Day 55) Positive EGFR expression (EGFR+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 1 mg/kg to thetail of each mouse.
In Vivo Model NCI-H1703 CDX model
In Vitro Model Lung squamous cell carcinoma NCI-H1703 cells CVCL_1490
IC1-MMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [18]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 84.30% (Day 25) Positive ICAM1 expression (ICAM1 +++/++)
Method Description
IC1-MMAE (5 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of MDA-MB-436 or MDA-MB-231 cells with ICAM1 expression with high expression.
In Vivo Model MDA-MB-231 CDX model
In Vitro Model Breast adenocarcinoma MDA-MB-231 cells CVCL_0062
Experiment 2 Reporting the Activity Date of This ADC [18]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.00% (Day 25) Positive ICAM1 expression (ICAM1 +++/++)
Method Description
IC1-MMAE (5 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of MDA-MB-436 or MDA-MB-231 cells with ICAM1 expression with high expression.
In Vivo Model MDA-MB-436 CDX model
In Vitro Model Metastasis of ductal carcinoma MDA-MB-436 cells CVCL_0623
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [18]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
7.30 pM
Positive ICAM1 expression (ICAM1 +++/++)
Method Description
In vitro cytotoxicity of four ICAM1 ADCs against a panel of four human TNBC cell lines.
In Vitro Model Metastasis of ductal carcinoma MDA-MB-436 cells CVCL_0623
Experiment 2 Reporting the Activity Date of This ADC [18]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
68.70 pM
Positive ICAM1 expression (ICAM1 +++/++)
Method Description
In vitro cytotoxicity of four ICAM1 ADCs against a panel of four human TNBC cell lines.
In Vitro Model Breast adenocarcinoma MDA-MB-468 cells CVCL_0419
Experiment 3 Reporting the Activity Date of This ADC [18]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.12 nM
Positive ICAM1 expression (ICAM1 +++/++)
Method Description
In vitro cytotoxicity of four ICAM1 ADCs against a panel of four human TNBC cell lines.
In Vitro Model Breast carcinoma MDA-MB-157 cells CVCL_0618
Anti-BCMA 15B2WT-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.16% (Day 21) Moderate BCMA expression (BCMA++)
Method Description
Mice were treated with either a single intravenous dose of ADCs at 1 mg/kg, or dosed intravenously with J6M0-mc-MMAF ADC weekly at a dose of 1 mg/kg for 3 weeks. Control mice were left untreated.
In Vivo Model JJN-3 CDX model
In Vitro Model Plasma cell myeloma JJN-3 cells CVCL_2078
AbA-mcMMAE [Investigative]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 33) Positive EGFR expression (EGFR+++/++)
Method Description
Cells were subcutaneously inoculated at a dose of 1,000,000 cells to the right flank region of each female nude mouse (Day 0). On the day 7 of grouping, the antibody-drug conjugate was intravenously administered at doses of 3 mg/kg to thetail of each mouse.
In Vivo Model EBC-1 CDX model
In Vitro Model Lung squamous cell carcinoma EBC-1 cells CVCL_2891
Anti-HER2-D265C-30.2867 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
29.00 pM
Positive HER2 expression (HER2 +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
57.00 pM
Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
7.08 nM
Moderate HER2 expression (HER2++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
Anti-PSMA-D265C-30.2867 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
47.00 pM
Positive PSMA expression (PSMA +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.49 nM
Positive PSMA expression (PSMA +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model Prostate carcinoma 22RV1 cells CVCL_1045
Anti-HER2-D265C-30.0880 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
47.00 pM
Positive HER2 expression (HER2+++/++; HER2 MFI=1016)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
58.00 pM
Positive HER2 expression (HER2 +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
86.00 nM
Moderate HER2 expression (HER2++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-HER2 antibody carrying a D265C mutation (T-D265C, anti-HER2-D265C) conjugated tostructurally different amanitin derivatives via its D265C residue was tested on JIMT-1 cells NCI-N87 cells and SKBR-3 cells.
In Vitro Model Breast ductal carcinoma JIMT-1 cells CVCL_2077
ZHER2-ABD-mcMMAF [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 5 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.01 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Invasive breast carcinoma BT-474 cells CVCL_0179
Experiment 2 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Breast adenocarcinoma AU565 cells CVCL_1074
Experiment 4 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
12.00 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Ovarian serous cystadenocarcinoma SK-OV-3 cells CVCL_0532
Experiment 5 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
215 nM
Moderate HER2 expression (HER2 ++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Lung adenocarcinoma A-549 cells CVCL_0023
B7H3-EC2 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.01 nM
High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 2 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 3 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
HER2-EC1 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.08 nM
High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 2 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
Experiment 3 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Anti-PSMA-D265C-30.0880 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.11 nM
Positive PSMA expression (PSMA +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model Prostate carcinoma LNCaP cells CVCL_0395
Experiment 2 Reporting the Activity Date of This ADC [19]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.57 nM
Positive PSMA expression (PSMA +++/++)
Method Description
The cytotoxic activity in vitro of ADCs, which are comprising an anti-PSMA antibody carrying a D265C mutation conjugated tostructurally different amanitin derivatives via its D265C residue was tested on LNCaP cells and 22RV1 cells.
In Vitro Model Prostate carcinoma 22RV1 cells CVCL_1045
B7H3-EC1 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.19 nM
High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 2 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 3 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
C4.4A-EC2 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.37 nM
High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 2 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
88.00 nM
High LYPD3 expression (LYPD3+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
Experiment 3 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
ZHER2-ABD-mcMMAE [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.20 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Breast adenocarcinoma SK-BR-3 cells CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC [20]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
24.00 nM
High HER2 expression (HER2 +++)
Method Description
HER2-expressing cell lines were incubated with concentration series of the drug conjugates, and the viability of the cells was measured.
In Vitro Model Breast adenocarcinoma AU565 cells CVCL_1074
C4.4A-EC1 [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.00 nM
High CD276 expression (CD276+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma MDA-MB-453 cells CVCL_0418
Experiment 2 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
240.00 nM
High LYPD3 expression (LYPD3+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Lung adenocarcinoma A549-C4.4a cells CVCL_0023
Experiment 3 Reporting the Activity Date of This ADC [21]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 10.00 uM High LYPD3 expression (LYPD3+++); High HER2 expression (HER2+++)
Method Description
The in vitro potency of NAMPTi-SMOLs and NAMPTi-ADCs was determined in human tumor cell lines. Cells (2000-4000 cells/well, were incubated at 37°C, 5% CO2 for 24 h and the compounds were added at concentrations of 3x10-12 - 3x10-8 Min triplicates. Cell viability was determined at the beginning (day 0) and after 72-96 h incubation in the presence or absence of NAMPTi-SMOLs or NAMPTi-ADCs.

   Click to Show/Hide
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
3A5-57 ADC [Investigative]
Revealed Based on the Cell Line Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Positive MUC16 expression (MUC16 +++/++)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [22]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 100 nM Negative MUC16 expression (MUC16-)
Method Description
Cells were seeded in 96 well plates at 3000 cells per well in complete growth media and grown overnight. For cell viability curves, serially diluted conjugates or payloads were added to the cells at final concentrations ranging from 300 nM to 5 pM and incubated for 8 days.
In Vitro Model Normal HEK293 cells CVCL_0045
AGS-16C3F [Terminated in phase 2]
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [23]
Efficacy Data Partial Response (PR)
23.08%
High ENPP3 expression (ENPP3+++)
Patients Enrolled
Metastatic renal cell carcinoma (MRCC), Eastern Cooperative Oncology Group (ECOG) performance status 1, adequate organ and bone marrow function.
Administration Dosage
AGS-16M8F was administered intravenously every 3 weeks at 5 dose levels ranging from 0.60 to 4.80 mg/kg until unacceptable toxicity or progression. A second study with AGS-16C3F started with the AGS-16M8F bridging dose of 4.80 mg/kg given every 3 weeks.
Related Clinical Trial
NCT Number NCT01672775  Clinical Status Phase 1
Clinical Description
A phase 1, open label, multi-center study to assess the safety, pharmacokinetics and effectiveness of AGS-16C3F monotherapy in subjects with renal cell carcinoma (RCC) of clear cell or papillary histology.
Primary Endpoint
In the AGS-16C3F study (n = 34),the MTD was 3.60 mg/kg,but this was not tolerated. The 1.80 mg/kg dose was determined to be safe and was associated antitumor response.
Other Endpoint
3 subjects at 1.80 mg/kg achieved durable PR (3/13, 23.08%). The disease control rate at 1.80 mg/kg was 92.30% (N=12/13). The disease control rate for the entire study was 58.82% (N=20/34).
Experiment 2 Reporting the Activity Date of This ADC [24]
Efficacy Data Objective Response Rate (ORR)
7.50% (AGS16C3F)
18.20% (axitinib)
Moderate ENPP3 expression (ENPP3++)
Patients Enrolled
Advanced renal cell carcinoma (RCC).
Administration Dosage
Intravenous AGS-16C3F 1.80 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose).
Related Clinical Trial
NCT Number NCT02639182  Clinical Status Phase 2
Clinical Description
A multi-center, open label, randomized phase 2 study of AGS-16C3F vs. axitinib in metastatic renal cell carcinoma.
Primary Endpoint
Median PFS=2.90 months (95% CI,2.00-4.00) for AGS16C3F,Median PFS=5.7 months (95% CI,5.30-9.10) for axitinib.
Other Endpoint
Disease Control Rate (DCR)=13.40% (95% CI,6.3-24.0) for AGS16C3F, Disease Control Rate (DCR)=22.70% (95% CI,13.30-34.70) for axitinib. Median duration of Response (mDoR)=6.80 months (95% CI,3.80-18.40) for AGS16C3F, Median duration of Response (mDoR)=6.7 months (95% CI,1.80-9.20) for axitinib. Objective Response Rate (ORR)=7.50% (95% CI,2.50-16.60) for AGS16C3F, Objective Response Rate (ORR)=18.20% (95% CI,9.80-29.60) for axitinib. Median Overall Survival (mOS)=13.10 months for AGS16C3F, Median Overall Survival (mOS)=15.40 months for axitinib.

   Click to Show/Hide
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.10 nM
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Normal ROSA KIT D816V cells CVCL_5G50
Experiment 2 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.73 nM
Moderate ENPP3 expression (ENPP3++)
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast-cell sarcoma ROSA KIT D816V Gluc cells Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
109.90 nM
High ENPP3 expression (ENPP3+++)
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast cell leukemia HMC-1.1 cells CVCL_H206
Experiment 4 Reporting the Activity Date of This ADC [25]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
146.50 nM
Method Description
Cells were incubated in triplicate in medium containing AGS-16C3F or cHmLYS-1c3.G2k-mcMMAF (0 [Control],0.001,0.003,0.008,0.02,0.07,0.21,0.62,1.82,5.57,16.67,50,150,450,and 1350 nM) in a 5% CO2 incubator at 37°C for 96 hours. IC50 values at day 5 for AGS-16C3F were calculated for each cell line.
In Vitro Model Mast cell leukemia HMC-1.2 cells CVCL_H205
MEDI-547 [Terminated in phase 1]
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [26]
Efficacy Data Objective Response Rate (ORR)
0.00%
Patients Enrolled
Malignant solid tumor thought to be associated with increased expression of EphA2 (endometrial, breast, ovarian, prostate, non-small cell lung, colon, esophageal, gastric, and bladder cancers, renal cell carcinoma, melanoma), relapsed or refractory to standard therapy, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

   Click to Show/Hide
Administration Dosage
0.08 mg/kg, 1-h intravenous (IV) infusion once q3wks or qwk for 3 consecutive weeks until unacceptable toxicity, progressive disease.
Related Clinical Trial
NCT Number NCT00796055  Clinical Status Phase 1
Clinical Description
A phase 1, open-label study of MEDI-547 to evaluate the safety, tolerability, pharmacokinetics, and biologic activity of intravenous administration in subjects with relapsed or refractory solid tumors associated with epha2 expression.
Primary Endpoint
Best response included progressive disease (n=5, 83.33%) and stable disease (n=1, 16.67%), No complete or partial tumor responses.
Other Endpoint
MTD could not be selected.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [27]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 48.00% Negative EPHA2 expression (EPHA2-)
Method Description
Mice injected with EphA2-negative SPEC-2 cell was assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
In Vivo Model Endometrial cancer CDX model
In Vitro Model Endometrial cancer Endometrial cancer cells Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC [27]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 86.67% Positive EPHA2 expression (EPHA2+++/++)
Method Description
Mice injected with either Hec-1A or Ishikawa were assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
In Vivo Model Endometrial cancer CDX model
In Vitro Model Endometrial adenocarcinoma HEC-1-A cells CVCL_0293
Experiment 3 Reporting the Activity Date of This ADC [27]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.00% Positive EPHA2 expression (EPHA2+++/++)
Method Description
Mice injected with either Hec-1A or Ishikawa were assigned to one of four groups (n = 10 mice per group),MEDI-547,3 mg/kg weekly.
In Vivo Model Endometrial cancer CDX model
In Vitro Model Endometrial adenocarcinoma Ishikawa cells CVCL_2529
PF-06263507 [Terminated in phase 1]
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [28]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.70% (Day 60) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of PF-06263507 was 3 mg/kg Q4D 4.

   Click to Show/Hide
In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC [28]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 60) Low 5T4 expression (5T4+)
Method Description
ASN004 was evaluated for efficacy in human tumor mouse xenograft models,derived from four different human tumor cell types,having a wide range of 5T4 expression levels. ASN004 was further evaluated in a tumor xenograft model derived from the H1975 human lung carcinoma cell line [5T4+; 15, 800 binding sites per cell]. Subcutaneous tumor xenografts were developed in nude mice with established mean tumor volumes of 150 mm3. The dose of PF-06263507 was 10 mg/kg Q4D 4.

   Click to Show/Hide
In Vivo Model Lung cancer CDX model
In Vitro Model Lung cancer Lung cancer cells Homo sapiens
References
Ref 1 Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 Dec;19(12):1641-1653.
Ref 2 Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.
Ref 3 Near-infrared photoimmunotherapy of cancer: a new approach that kills cancer cells and enhances anti-cancer host immunity. Int Immunol. 2021 Jan 1;33(1):7-15.
Ref 4 Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035.
Ref 5 Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial. Neuro Oncol. 2023 Feb 14;25(2):339-350. doi: 10.1093/neuonc/noac173.
Ref 6 Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289. doi: 10.3390/ph13100289.
Ref 7 Phase I/II Open Label Dose Escalation and Dose Expansion Study of Intravenous Infusion of W0101, an Antibody-drug Conjugate, in Patients With Advanced or Metastatic Solid Tumors. International, Multicenter, Open Label Study, NCT03316638
Ref 8 Efficacy of the Antibody-Drug Conjugate W0101 in Preclinical Models of IGF-1 Receptor Overexpressing Solid Tumors. Mol Cancer Ther. 2020 Jan;19(1):168-177.
Ref 9 An Open-label, Phase 1, Dose-escalation Study to Evaluate the Safety and Preliminary Antitumor Activity of TAK-676 With Pembrolizumab Following Radiation Therapy in the Treatment of Non-small-cell Lung Cancer, Triple-negative Breast Cancer, or Squamous-cell Carcinoma of the Head and Neck That Has Progressed on Checkpoint Inhibitors
Ref 10 An Open-label, Dose Escalation, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TAK-676 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors
Ref 11 Anti-tumor activity of antibody drug conjugate targeting aspartate--hydroxylase in pancreatic ductal adenocarcinoma. Cancer Lett. 2019 May 1;449:87-98. doi: 10.1016/j.canlet.2019.02.006. Epub 2019 Feb 12.
Ref 12 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.
Ref 13 Anti-huLRRC15 antibody drug conjugates and methods for their use. 2017-06-08
Ref 14 Bcma monoclonal antibody-drug conjugate.
Ref 15 Anti-egfr antibodies and antibody drug conjugates.
Ref 16 Antibody drug conjugates against the receptor for advanced glycation end products (RAGE), a novel therapeutic target in endometrial cancer. J Immunother Cancer. 2019 Oct 29;7(1):280. doi: 10.1186/s40425-019-0765-z.
Ref 17 Hydrophilic antibody-drug conjugates; 2015-08-20.
Ref 18 A rationally designed ICAM1 antibody drug conjugate eradicates late-stage and refractory triple-negative breast tumors in vivo. Sci Adv. 2023 May 5;9(18):eabq7866. doi: 10.1126/sciadv.abq7866. Epub 2023 May 5.
Ref 19 Amatoxin antibody-drug conjugates and uses thereof; 2020-10-29.
Ref 20 Comparison of HER2-targeted affibody conjugates loaded with auristatin- and maytansine-derived drugs. J Control Release. 2023 Mar;355:515-527. doi: 10.1016/j.jconrel.2023.02.005. Epub 2023 Feb 14.
Ref 21 A Novel NAMPT Inhibitor-Based Antibody-Drug Conjugate Payload Class for Cancer Therapy. Bioconjug Chem. 2022 Jun 15;33(6):1210-1221.
Ref 22 Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids. Bioorg Med Chem. 2020 Dec 1;28(23):115785. doi: 10.1016/j.bmc.2020.115785. Epub 2020 Oct 11.
Ref 23 Phase I Trials of Anti-ENPP3 Antibody-Drug Conjugates in Advanced Refractory Renal Cell Carcinomas. Clin Cancer Res. 2018 Sep 15;24(18):4399-4406.
Ref 24 A Randomized Phase II Study of AGS-16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma. Oncologist. 2021 Mar;26(3):182-e361.
Ref 25 In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis. Blood Adv. 2019 Feb 26;3(4):633-643.
Ref 26 Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors. Invest New Drugs. 2013 Feb;31(1):77-84.
Ref 27 EphA2 targeted chemotherapy using an antibody drug conjugate in endometrial carcinoma. Clin Cancer Res. 2010 May 1;16(9):2562-70.
Ref 28 ASN004, A 5T4-targeting scFv-Fc Antibody-Drug Conjugate with High Drug-to-Antibody Ratio, Induces Complete and Durable Tumor Regressions in Preclinical Models. Mol Cancer Ther. 2021 Aug;20(8):1327-1337.

If you find any error in data or bug in web service, please kindly report it to Dr. Shen et al.