Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0MCWQA
|
|||||
|---|---|---|---|---|---|---|
| ADC Name |
Enapotamab vedotin
|
|||||
| Synonyms |
enapotamab vedotin; HuMax-AXL-ADC; AXL-107-MMAE
Click to Show/Hide
|
|||||
| Organization |
Genmab (Originator)
|
|||||
| Drug Status |
Phase 1/2 (discontinued)
|
|||||
| Drug-to-Antibody Ratio |
4
|
|||||
| Structure |
|
|||||
|
|
||||||
| Antibody Name |
Enapotamab
|
Antibody Info | ||||
| Antigen Name |
Tyrosine-protein kinase receptor UFO (AXL)
|
Antigen Info | ||||
| Payload Name |
MMAE
|
Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
|
Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
|
Linker Info | ||||
| Conjugate Type |
Random Cysteines
|
|||||
| Combination Type |
vedotin
|
|||||
The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||
|---|---|---|---|---|---|---|---|---|---|
| Cervical cancer |
1 Trials
|
||||||||
| Endometrial cancer |
1 Trials
|
||||||||
| Lung cancer |
1 Trials
|
||||||||
| Melanoma |
1 Trials
|
||||||||
| Ovarian cancer |
1 Trials
|
||||||||
| Sarcomas |
1 Trials
|
||||||||
| Thyroid cancer |
1 Trials
|
||||||||
| Unspecific solid tumor |
1 Trials
|
General Information of The Activity Data Related to This ADC
Discovered Using Patient-derived Xenograft Model
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line Data
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 0% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFE772; EGFR mutation) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 6% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Antitumor activity of EnaV in Nonresponder.
|
||||
| In Vivo Model | NSCLC PDX model | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 13.30% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (0.30 mg/kg,q.d.). Enapotamab vedotin and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
|
||||
| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 16.50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU0858; EGFR L858R mutation) | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 16.50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU2511; EGFR mutation) | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 29.60% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
EnaV=2 mg/kg.
|
||||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU0395) | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 46.90% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
EnaV=4 mg/kg.
|
||||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU0395) | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LCx-MR007; Osimertinib resistant) | ||||
| Experiment 9 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU1868; EGFR L858R and T790Mmutations) | ||||
| Experiment 10 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFA677; EGFR mutation) | ||||
| Experiment 11 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 56.40% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Antitumor activity of EnaV in intermediate.
|
||||
| In Vivo Model | NSCLC PDX model | ||||
| Experiment 12 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 60% | Moderate AXL expression (AXL++; IHC H-score=121) | ||
| Method Description |
EnaV=4 mg/kg.
|
||||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU2511) | ||||
| Experiment 13 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 66.50% | Moderate AXL expression (AXL++; IHC H-score=101) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFA526) | ||||
| Experiment 14 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 67% | High AXL expression (AXL+++; IHC H-score=248) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LU0395; EGFR mutation) | ||||
| Experiment 15 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 72.70% | Moderate AXL expression (AXL++; IHC H-score=142) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas ,esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 2 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFA526) | ||||
| Experiment 16 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 84.10% | Moderate AXL expression (AXL++; IHC H-score=141) | ||
| Method Description |
The anti-tumor activity of ADCs were determined in the pancreas cancer patient-derived xenograft (PDX) model PAXF1657. Before treatment,mice were divided into groups of 68 mice each,with equal tumor size distribution (average and variance). ADC is administered at a dose of 2.00 mg/kg in a single dose.
|
||||
| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 17 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.80% | Moderate AXL expression (AXL++; IHC H-score=183) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas, esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 2 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Cervical cancer PDX model (PDX: CV1664) | ||||
| Experiment 18 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97.40% | Moderate AXL expression (AXL++; IHC H-score=104) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas, esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 4 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Cervical cancer PDX model (PDX: CV1664) | ||||
| Experiment 19 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.30% | Negative AXL expression (AXL-; IHC H-score=0) | ||
| Method Description |
The anti-tumor activity of ADCs were determined in the pancreas cancer patient-derived xenograft (PDX) model PAXF1657. Before treatment,mice were divided into groups of 68 mice each,with equal tumor size distribution (average and variance). ADC is administered at a dose of 4.00 mg/kg in a single dose.
|
||||
| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 20 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.30% | High AXL expression (AXL+++; IHC H-score=305) | ||
| Method Description |
The antitumor activity of ADCT-601 was tested in a range of human solid tumor xenograft models covering multiple indications. Single-dose (4 mg/kg,q.d.). Enapotamab vedotin and isotype-control ADC (B12-PL1601) were administered intravenously (day 1) to treatment groups of 8 mice.
|
||||
| In Vivo Model | Pancreatic cancer PDX model (PDX: PAXF1657) | ||||
| Experiment 21 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.80% | Moderate AXL expression (AXL++; IHC H-score=117) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas, esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 4 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFA526) | ||||
| Experiment 22 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | Non-small cell lung cancer PDX model (PDX: LXFA677_R, EGFRi resistant) | ||||
| Experiment 23 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Antitumor activity of EnaV in responder.
|
||||
| In Vivo Model | NSCLC PDX model | ||||
| Experiment 24 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 70.55 ng/mL | Moderate AXL expression (AXL++; 22,304 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vivo Model | Melanoma PDX model (PDX: M019R.X1.CL) | ||||
| In Vitro Model | Melanoma | M019R.X1.CL cells | Homo sapiens | ||
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 1% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with MART-1 T cells.
|
||||
| In Vivo Model | SkMel-147 cell line xenograft model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 17.70% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with MART-1 T cells + Ctrl ADC.
|
||||
| In Vivo Model | SkMel-147 cell line xenograft model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 34.30% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
EnaV=2 mg/kg.
|
||||
| In Vivo Model | LU2511 in NSCLC CDX model | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 40.90% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
EnaV=0.5 mg/kg.
|
||||
| In Vivo Model | LCLC-103H in NSCLC CDX model | ||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 43.40% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with MART-1 T cells.
|
||||
| In Vivo Model | LCLC-103H xenograft model | ||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 64% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with Ctrl T cells + EnaV.
|
||||
| In Vivo Model | SkMel-147 cell line xenograft model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 64.70% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with MART-1 T cells.
|
||||
| In Vivo Model | BLM cell line xenograft model | ||||
| In Vitro Model | Amelanotic melanoma | BLM cells | CVCL_7035 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 66.50% | Positive AXL expression (AXL+++/++) | ||
| In Vivo Model | LCLC-103H CDX model | ||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 78.50% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas, esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 2 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Melanoma CDX model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 10 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 85.20% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
Treated with MART-1 T cells + EnaV.
|
||||
| In Vivo Model | SkMel-147 cell line xenograft model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 92.70% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
In the LCLC-103H xenograft model,therapeutic treatment with a single dose of 1 mg/kg in anti-tumor activity in the AXL-ADC panel.
|
||||
| In Vivo Model | Lung cancer CDX model | ||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 12 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 93.60% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
The in vivo activity of Enapotamab vedotin was evaluated in additional cell line-derived and patient-derived xenograft (PDX) models representing different cancer types, including pancreas, esophageal, lung, thyroid, ovarian, cervical cancer, melanoma and sarcoma. Enapotamab vedotin was administered at a dose of 4 mg/kg once a week for two weeks.
|
||||
| In Vivo Model | Melanoma CDX model | ||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 13 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | 96.80% | Positive AXL expression (AXL+++/++) | ||
| Method Description |
EnaV=1 mg/kg.
|
||||
| In Vivo Model | LCLC-103H in NSCLC CDX model | ||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.08 nM | High AXL expression (AXL+++) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 2 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.09 nM | Moderate AXL expression (AXL++) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Lung adenocarcinoma | PC-9 cells | CVCL_B260 | ||
| Experiment 3 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.09 nM | High AXL expression (AXL+++) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 4 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.17 nM | High AXL expression (AXL+++) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Lung squamous cell carcinoma | Calu-1 cells | CVCL_0608 | ||
| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Low AXL expression (AXL+) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Breast adenocarcinoma | MDA-MB-453 cells | CVCL_0418 | ||
| Experiment 6 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 100 nM | Low AXL expression (AXL+) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Lung large cell carcinoma | NCI-H460 cells | CVCL_0459 | ||
| Experiment 7 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 5.5 ng/mL | Moderate AXL expression (AXL++; 37,235 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Melanoma | A-875 cells | CVCL_4733 | ||
| Experiment 8 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 15.34 ng/mL | Moderate AXL expression (AXL++; 54,946 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Cutaneous melanoma | SK-MEL-28 cells (BRAF inhibitor resistant) | CVCL_0526 | ||
| Experiment 9 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 20.7 ng/mL | High AXL expression (AXL+++; 117,665 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Lung large cell carcinoma | LCLC-103H cells | CVCL_1375 | ||
| Experiment 10 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 24.3 ng/mL | Moderate AXL expression (AXL++; 46,701 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Breast adenocarcinoma | MDA-MB-231 cells | CVCL_0062 | ||
| Experiment 11 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 42.06 ng/mL | Moderate AXL expression (AXL++; 35,452 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Melanoma | SK-MEL-147 cells | CVCL_3876 | ||
| Experiment 12 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 68.54 ng/mL | High AXL expression (AXL+++; 169,192 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Lung squamous cell carcinoma | Calu-1 cells | CVCL_0608 | ||
| Experiment 13 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 189.3 ng/mL | Moderate AXL expression (AXL++; 70,222 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Melanoma | SK-MEL-2 cells (MEK inhibitor-resistant) | CVCL_0069 | ||
| Experiment 14 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 190.9 ng/mL | Moderate AXL expression (AXL++; 83,986 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Skin squamous cell carcinoma | A431 cells | CVCL_0037 | ||
| Experiment 15 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 370.4 ng/mL | Moderate AXL expression (AXL++; 16,611 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Amelanotic melanoma | A375/R cells | CVCL_IW10 | ||
| Experiment 16 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 887.2 ng/mL | Moderate AXL expression (AXL++; 16,611 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vivo Model | Melanoma PDX model (PDX: M016.X1.CL) | ||||
| In Vitro Model | Cutaneous melanoma | SK-MEL-5 cells | CVCL_0527 | ||
| Experiment 17 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 1828.3 ng/mL | Moderate AXL expression (AXL++; 66,691 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Lung large cell carcinoma | NCI-H1299 cells | CVCL_0060 | ||
| Experiment 18 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 2090.3 ng/mL | Moderate AXL expression (AXL++; 34,978 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Ovarian serous cystadenocarcinoma | SK-OV-3 cells | CVCL_0532 | ||
| Experiment 19 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 2895.7 ng/mL | Moderate AXL expression (AXL++; 28,000 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Pancreatic ductal adenocarcinoma | BxPC-3 cells | CVCL_0186 | ||
| Experiment 20 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 6881 ng/mL | Low AXL expression (AXL+; 9,138 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Lung large cell carcinoma | NCI-H661 cells | CVCL_1577 | ||
| Experiment 21 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Negative AXL expression (AXL-; 100 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Melanoma | SK-MEL-2 cells | CVCL_0069 | ||
| Experiment 22 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Negative AXL expression (AXL-; 325 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Cutaneous melanoma | SK-MEL-28 cells | CVCL_0526 | ||
| Experiment 23 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Negative AXL expression (AXL-; 250 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Cutaneous melanoma | SK-MEL-5 cells | CVCL_0527 | ||
| Experiment 24 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Negative AXL expression (AXL-; 150 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Gastric tubular adenocarcinoma | NCI-N87 cells | CVCL_1603 | ||
| Experiment 25 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Low AXL expression (AXL+; 2,326 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Pancreatic ductal adenocarcinoma | HPAF-II cells | CVCL_0313 | ||
| Experiment 26 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Moderate AXL expression (AXL++; 37,506 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Pleural epithelioid mesothelioma | NCI-H226 cells | CVCL_1544 | ||
| Experiment 27 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | > 10 ug/mL | Negative AXL expression (AXL-; 528 AXL receptor copy number) | ||
| Method Description |
All cell lines except melanoma were seeded at 1 x103 cells per well in 96 well culture plates (Greiner) and incubated for 3 h at 37°C, 5% CO2.
|
||||
| In Vitro Model | Colon adenocarcinoma | LS174T cells | CVCL_1384 | ||
| Experiment 28 Reporting the Activity Date of This ADC | [5] | ||||
| Efficacy Data | Half Maximal Inhibitory Concentration (IC50) | 0.2 . | Moderate AXL expression (AXL++) | ||
| Method Description |
Tumor cells were plated in 96-well plates at predetermined density, treated with AXL02-MMAE or hIgG1-MMAE for 5-8 days to ensure that the doubling of the cells is sufficient. Then MTS reagent solution was added with replacing fresh medium, and cells were incubated for an appropriate time.
|
||||
| In Vitro Model | Glioblastoma | U-87MG cells | CVCL_0022 | ||
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
19%
|
|||
| Patients Enrolled |
Eligible participants must have advanced/metastatic solid tumors refractory to standard therapy, measurable disease, and adequate organ function (ECOG 0-1). Exclusions cover uncontrolled cardiac disease, recent thrombosis, active infections, prior auristatin therapy, major surgery within 4 weeks, pregnancy, and significant comorbidities (e.g., Grade 2+ neuropathy, pneumonitis).
Click to Show/Hide
|
||||
| Administration Dosage |
Participants in all cohorts of the trial (both in escalation and expansion phase) will be administered enapotamab vedotin (HuMax-AXL-ADC) intravenously (IV).
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02988817 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors | ||||
| Primary Endpoint |
Safety measures include dose-limiting toxicities (DLTs) during Cycle 1 (Grade 4 hematologic events, severe non-hematologic AEs, and infusion reactions) and treatment-emergent adverse events (TEAEs), including serious events (TESAEs), ≥Grade 3 toxicities per NCI-CTCAE v4.03, and lab abnormalities, monitored up to 1130 days post-dose.
|
||||
| Other Endpoint |
Pharmacokinetic analysis evaluates conjugated enapotamab vedotin and free MMAE parameters (AUC0-inf, AUC0-last, Cmax, CL, Tmax, t1/2, Vss) across dosing regimens (1Q3W, 3Q4W). Secondary outcomes include ADA development and efficacy metrics (OR per RECIST v1.1, CA-125 response, DoR, PFS, OS, AXL expression changes) in solid tumor patients.
|
||||
| Experiment 2 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Disease control rate (DCR) |
50%
|
|||
| Patients Enrolled |
Eligible participants must have advanced/metastatic solid tumors refractory to standard therapy, measurable disease, and adequate organ function (ECOG 0-1). Exclusions cover uncontrolled cardiac disease, recent thrombosis, active infections, prior auristatin therapy, major surgery within 4 weeks, pregnancy, and significant comorbidities (e.g., Grade 2+ neuropathy, pneumonitis).
Click to Show/Hide
|
||||
| Administration Dosage |
Participants in all cohorts of the trial (both in escalation and expansion phase) will be administered enapotamab vedotin (HuMax-AXL-ADC) intravenously (IV).
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT02988817 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors | ||||
| Primary Endpoint |
Safety measures include dose-limiting toxicities (DLTs) during Cycle 1 (Grade 4 hematologic events, severe non-hematologic AEs, and infusion reactions) and treatment-emergent adverse events (TEAEs), including serious events (TESAEs), ≥Grade 3 toxicities per NCI-CTCAE v4.03, and lab abnormalities, monitored up to 1130 days post-dose.
|
||||
| Other Endpoint |
Pharmacokinetic analysis evaluates conjugated enapotamab vedotin and free MMAE parameters (AUC0-inf, AUC0-last, Cmax, CL, Tmax, t1/2, Vss) across dosing regimens (1Q3W, 3Q4W). Secondary outcomes include ADA development and efficacy metrics (OR per RECIST v1.1, CA-125 response, DoR, PFS, OS, AXL expression changes) in solid tumor patients.
|
||||
References