Linker Information
General Information of This Linker
Linker ID |
LIN0TAFAV
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Linker Name |
Maleimido-caproyl
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Linker Type |
Flexible reactive (thiol) linker
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Antibody-Linker Relation |
Uncleavable
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Structure | ||||||
Formula |
C10H13NO4
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Isosmiles |
O=C(O)CCCCCN1C(=O)C=CC1=O
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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)
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InChIKey |
WOJKKJKETHYEAC-UHFFFAOYSA-N
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Pharmaceutical Properties |
Molecule Weight
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211.217
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Polar area
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74.68
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Complexity
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15
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xlogp Value
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0.5564
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Heavy Count
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15
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Rot Bonds
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6
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Hbond acc
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3
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Hbond Donor
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1
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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
Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
Efficacy Data | Objective Response Rate (ORR) |
60.00%
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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.
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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.
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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.
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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%).
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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).
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Experiment 2 Reporting the Activity Date of This ADC | [2] | ||||
Efficacy Data | Objective Response Rate (ORR) |
60.00%
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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.
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Administration Dosage |
GSK2857916 3.4 mg/kg was administered through 1-h intravenous infusions once every 3 weeks, for a maximum of 16 cycles.
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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.
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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.
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Other Endpoint |
The median progression-free survival was 12.00 months and the median duration of response was 14.30 months.
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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.
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Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
Efficacy Data | Half Maximal Effective Concentration (EC50) |
30.60 ug/mL
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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).
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In Vitro Model | Thymoma | EL4 cells (BCMA expression) | CVCL_0255 |
Depatuxizumab mafodotin [Phase 3]
Identified from the Human Clinical Data
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)
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High EGFR expression (EGFR +++) | ||
Patients Enrolled |
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
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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.
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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)
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High EGFR expression (EGFR +++) | ||
Patients Enrolled |
EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
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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.
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Revealed Based on the Cell Line Data
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.
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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
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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.
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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
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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.
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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
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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.
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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
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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.
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In Vitro Model | Pleural mesothelioma | NCI-H2052 cells | CVCL_1518 |
Lonigutamab ugodotin [Phase 2]
Identified from the Human Clinical Data
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.
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Revealed Based on the Cell Line Data
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.
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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.
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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.
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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.
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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
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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.
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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
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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.
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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.
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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.
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In Vitro Model | Lung small cell carcinoma | SBC-5 cells | CVCL_1679 |
TAK-500 [Phase 1]
Identified from the Human Clinical Data
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.
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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.
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SNS-622-DM1 [Investigative]
Discovered Using Patient-derived Xenograft Model
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.
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In Vivo Model | Pancreatic ductal adenocarcinoma PDX model |
Discovered Using Cell Line-derived Xenograft Model
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.
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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
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.
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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.
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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.
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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 | [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.
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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 | [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.
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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
Experiment 1 Reporting the Activity Date of This ADC | [13] | ||||
Efficacy Data | Tumor Growth Inhibition value (TGI) |
0.00%
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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.
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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)
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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.
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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
Experiment 1 Reporting the Activity Date of This ADC | [13] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.01 nM - 0.10 nM
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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.
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In Vitro Model | Colon carcinoma | HCT 116 cells | CVCL_0291 |
Anti-BCMA J6M0-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
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.
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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.
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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.
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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.
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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
Experiment 1 Reporting the Activity Date of This ADC | [14] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
29.28 nM
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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.
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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
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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.
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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
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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.
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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
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.
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||||
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
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.
|
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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
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.
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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
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.
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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
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.
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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
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.
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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.
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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
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.
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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.
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In Vitro Model | Renal cell carcinoma | 786-O cells | CVCL_1051 |
hBU12-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
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.
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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.
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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
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.
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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.
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In Vitro Model | Renal cell carcinoma | 786-O cells | CVCL_1051 |
Ab1-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
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.
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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.
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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
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.
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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.
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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
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.
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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.
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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.
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In Vitro Model | Breast carcinoma | MDA-MB-157 cells | CVCL_0618 |
Anti-BCMA 15B2WT-mcMMAF [Investigative]
Discovered Using Cell Line-derived Xenograft Model
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.
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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
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
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.
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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.
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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.
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In Vitro Model | Breast ductal carcinoma | JIMT-1 cells | CVCL_2077 |
Anti-PSMA-D265C-30.2867 [Investigative]
Revealed Based on the Cell Line Data
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.
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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.
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In Vitro Model | Prostate carcinoma | 22RV1 cells | CVCL_1045 |
Anti-HER2-D265C-30.0880 [Investigative]
Revealed Based on the Cell Line Data
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.
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||||
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.
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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
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.
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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.
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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.
|
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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.
|
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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
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.
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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.
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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.
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In Vitro Model | Lung adenocarcinoma | A549-C4.4a cells | CVCL_0023 |
HER2-EC1 [Investigative]
Revealed Based on the Cell Line Data
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.
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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.
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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.
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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
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.
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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.
|
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In Vitro Model | Prostate carcinoma | 22RV1 cells | CVCL_1045 |
B7H3-EC1 [Investigative]
Revealed Based on the Cell Line Data
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.
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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.
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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.
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In Vitro Model | Lung adenocarcinoma | A549-C4.4a cells | CVCL_0023 |
C4.4A-EC2 [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
0.37 nM
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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.
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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
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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.
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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.
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In Vitro Model | Childhood acute monocytic leukemia | THP-1 cells | CVCL_0006 |
ZHER2-ABD-mcMMAE [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [20] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
8.20 nM
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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.
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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
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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.
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In Vitro Model | Breast adenocarcinoma | AU565 cells | CVCL_1074 |
C4.4A-EC1 [Investigative]
Revealed Based on the Cell Line Data
Experiment 1 Reporting the Activity Date of This ADC | [21] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
10.00 nM
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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.
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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
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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.
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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.
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In Vitro Model | Childhood acute monocytic leukemia | THP-1 cells | CVCL_0006 |
3A5-57 ADC [Investigative]
Revealed Based on the Cell Line Data
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.
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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.
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In Vitro Model | Normal | HEK293 cells | CVCL_0045 |
AGS-16C3F [Terminated in phase 2]
Identified from the Human Clinical Data
Experiment 1 Reporting the Activity Date of This ADC | [23] | ||||
Efficacy Data | Partial Response (PR) |
23.08%
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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.
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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.
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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.
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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.
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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).
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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).
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Administration Dosage |
Intravenous AGS-16C3F 1.80 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose).
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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.
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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.
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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.
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Discovered Using Cell Line-derived Xenograft Model
Experiment 1 Reporting the Activity Date of This ADC | [25] | ||||
Efficacy Data | Half Maximal Inhibitory Concentration (IC50) |
1.10 nM
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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.
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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
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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.
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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
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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.
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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
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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.
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In Vitro Model | Mast cell leukemia | HMC-1.2 cells | CVCL_H205 |
MEDI-547 [Terminated in phase 1]
Identified from the Human Clinical Data
Experiment 1 Reporting the Activity Date of This ADC | [26] | ||||
Efficacy Data | Objective Response Rate (ORR) |
0.00%
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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.
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Administration Dosage |
0.08 mg/kg, 1-h intravenous (IV) infusion once q3wks or qwk for 3 consecutive weeks until unacceptable toxicity, progressive disease.
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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.
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Primary Endpoint |
Best response included progressive disease (n=5, 83.33%) and stable disease (n=1, 16.67%), No complete or partial tumor responses.
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Other Endpoint |
MTD could not be selected.
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Discovered Using Cell Line-derived Xenograft Model
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.
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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.
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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.
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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
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.
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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.
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In Vivo Model | Lung cancer CDX model | ||||
In Vitro Model | Lung cancer | Lung cancer cells | Homo sapiens |
References
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