Payload Information

General Information of This Payload
Payload ID
PAY0WDZAK
Name
Auristatin 0101
Synonyms
PF-06380101; 1436391-86-4; Auristatin 0101; Aur0101; Q8020AX34E; AUR-0101; 2-Methyl-L-Alanyl-N-[(3r,4s,5s)-3-Methoxy-1-{(2s)-2-[(1r,2r)-1-Methoxy-2-Methyl-3-Oxo-3-{[(1s)-2-Phenyl-1-(1,3-Thiazol-2-Yl)ethyl]amino}propyl]pyrrolidin-1-Yl}-5-Methyl-1-Oxoheptan-4-Yl]-N-Methyl-L-Valinamide; (2S)-2-((2-Amino-2-methyl-propanoyl)amino)-N-((1S,2R)-2-methoxy-4-((2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-(((1S)-2-phenyl-1-thiazol-2-yl-ethyl)amino)propyl)pyrrolidin-1-yl)-1-((1S)-1-methylpropyl)-4-oxo-butyl)-N,3-dimethyl-butanamide; (S)-2-(2-amino-2-methylpropanamido)-N-((3R,4S,5S)-3-methoxy-1-((S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-(((S)-2-phenyl-1-(thiazol-2-yl)ethyl)amino)propyl)pyrrolidin-1-yl)-5-methyl-1-oxoheptan-4-yl)-N,3-dimethylbutanamide; L-Valinamide, 2-methylalanyl-N-((1S,2R)-2-methoxy-4-((2S)-2-((1R,2R)-1-methoxy-2-methyl-3-oxo-3-(((1S)-2-phenyl-1-(2-thiazolyl)ethyl)amino)propyl)-1-pyrrolidinyl)-1-((1S)-1-methylpropyl)-4-oxobutyl)-N-methyl-; Auristatin-0101; UNII-Q8020AX34E; CHEMBL3359827; SCHEMBL14936149; AKOS040742399; CS-3706; NCGC00485972-01; HY-12522; MS-31297; F85106; Q27454197; (2S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide; 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide; 3WD
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Target(s) Microtubule (MT)
 Target Info 
Structure
Formula
C39H62N6O6S
Isosmiles
CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C3=NC=CS3)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)C(C)(C)N
PubChem CID
71569947
InChI
InChI=1S/C39H62N6O6S/c1-11-25(4)33(44(8)37(48)32(24(2)3)43-38(49)39(6,7)40)30(50-9)23-31(46)45-20-15-18-29(45)34(51-10)26(5)35(47)42-28(36-41-19-21-52-36)22-27-16-13-12-14-17-27/h12-14,16-17,19,21,24-26,28-30,32-34H,11,15,18,20,22-23,40H2,1-10H3,(H,42,47)(H,43,49)/t25-,26+,28-,29-,30+,32-,33-,34+/m0/s1
InChIKey
QAAFNSMAIAVCHE-BZLYQNAUSA-N
IUPAC Name
(2S)-2-[(2-amino-2-methylpropanoyl)amino]-N-[(3R,4S,5S)-3-methoxy-1-[(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino]propyl]pyrrolidin-1-yl]-5-methyl-1-oxoheptan-4-yl]-N,3-dimethylbutanamide
Pharmaceutical Properties
Molecule Weight
743
Polar area
184
Complexity
1170
xlogp Value
4.1
Heavy Count
52
Rot Bonds
19
Hbond acc
9
Hbond Donor
3
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 0.8 nM
HT-29 cells
Colon adenocarcinoma
CVCL_0320 
[1]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
Cofetuzumab pelidotin [Phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Partial Response (PR)
16.67%
Patients Enrolled
Metastatic TNBC or ER low (ER and PgR <5%, HER2 negative) breast cancer, and had received at least one prior chemotherapy for metastatic disease.
Administration Dosage
Gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks, 180 mg + 1.4 mg/kg, and 180 mg + 2.8 mg/kg.
Related Clinical Trial
NCT Number NCT03243331  Phase Status Phase 1
Clinical Description
An initial safety study of gedatolisib plus PTK7-ADC for metastatic triple-negative breast cancer.
Primary Endpoint
A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly cofetuzumab pelidotin 1.40 mg/kg every 3 weeks (n=4), 180 mg, 1.40 mg/kg (n=3), and 180 mg, 2.80 mg/kg (n=11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached grade 3 severity. Myelosuppression was uncommon. ORR was 16.67% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for>18 weeks); CB18 was 27.80%. Median PFS was 2.00 months (95% confidence interval for PFS: 1.20-6.20). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.

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Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
27.00% (Ovarian cancer, every 3 weeks)
16.00% (NSCLC, every 3 weeks)
21.00% (TNBC, every 3 weeks)
26.00% (Ovarian cancer, every 2 weeks)
33.00% (NSCLC, every 2 weeks)
Patients Enrolled
Locally advanced or metastatic solid tumors resistant to standard therapy or with no available standard therapy, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Administration Dosage
Intravenously every 3 weeks at 0.20-3.70 mg/kg or every 2 weeks at 2.10-3.20 mg/kg.
Related Clinical Trial
NCT Number NCT02222922  Phase Status Phase 1
Clinical Description
A first-in-human phase 1, dose escalation, safety and pharmacokinetic study of PF-06647020 in adult patients with advanced solid tumors.
Primary Endpoint
The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia,fatigue, headache, neutropenia, and vomiting (45%); 25% of patients had grade 3 neutropenia. Two patients experienced doselimiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.80 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27.00% in ovarian cancer (n=63), 19% in NSCLC (n=31), and 21% in TNBC (n=29).

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Experiment 3 Reporting the Activity Date of This ADC [5]
Related Clinical Trial
NCT Number NCT04189614  Phase Status Phase 1
Clinical Description
A phase 1b efficacy and safety study of cofetuzumab pelidotin (ABBV-647, a PTK7-targeting antibody drug conjugate) in subjects with PTK7-expressing, recurrent non-small cell lung cancer.
PYX-201 [Phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT05720117  Phase Status Phase 1
Clinical Description
A first-in-human, open-label, multicenter, phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PYX-201 in participants with advanced solid tumors.
PF-06804103 [Phase 1]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00%
High HER2 expression (HER2+++)
Method Description
In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 1 x106 NCI-N87, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm3. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).

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In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC [6]
Efficacy Data Tumor Growth Inhibition value (TGI)
100.00%
Moderate HER2 expression (HER2++)
Method Description
In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 10 x106 BT474 cells, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm3. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).

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In Vitro Model Invasive breast carcinoma BT474-M1 cells CVCL_0179
EDB-ADC [Investigative]
 ADC Info 
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 0.00% (Day 14) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 0.75 mg/kg q4dx4.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-PAX-13565)
Experiment 2 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 26.20% (Day 14) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 1.5 mg/kg q4dx4.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-PAX-13565)
Experiment 3 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 43.20% (Day 28) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 0.3 mg/kg q4dx4.
In Vivo Model Nonsmall cell lung cancer PDX model (PDX: PDX-NSX-11122)
Experiment 4 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 79.30% (Day 28) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 1 mg/kg q4dx4.
In Vivo Model Nonsmall cell lung cancer PDX model (PDX: PDX-NSX-11122)
Experiment 5 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 87.80% (Day 14) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 3 mg/kg q4dx4.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-PAX-13565)
Experiment 6 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.20% (Day 28) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Mice were treated intravenously every 4 days with phosphate-buffered saline (PBS),Neg-vc0101 (Neg-ADC),EDC-vc0101 (EDB-ADC). This tumor model was injected intravenously with EDB-ADC 3 mg/kg q4dx4.
In Vivo Model Nonsmall cell lung cancer PDX model (PDX: PDX-NSX-11122)
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 67.00% (Day 15) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Athymic nu/nu nude mice were injected subcutaneously in the right flank with 8 10 6 cells suspended in 100% Matrigel. This tumor model was injected intravenously with EDB-ADC 1 mg/kg q4dx4.
In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Experiment 2 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 80.10% (Day 15) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Athymic nu/nu nude mice were injected subcutaneously in the right flank with 8 10 6 cells suspended in 100% Matrigel. This tumor model was injected intravenously with EDB-ADC 3 mg/kg q4dx4.
In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Experiment 3 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 30) High FN1 expression (FN1+++)
Method Description
EDB+FN expression was evaluated in NSCLC and pancreatic cancer xenografts in immunocompromised mice using IHC. Athymic nu/nu nude mice were injected subcutaneously in the right flank with 8 10 6 cells suspended in 100% Matrigel. This tumor model was injected intravenously with EDB-ADC 3 mg/kg q4dx4.
In Vitro Model Lung adenocarcinoma NCI-H1975 cells CVCL_1511
Anti-IL13RA2-ADC [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [8]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 29.60% (Day 13) High IL13RA2 expression (IL13RA2+++)
Method Description
2 x106 A375 cells in 50% Cultrex basement membrane extract were injected subcutaneously in the flank of athymic nu/nu mice for FMT imaging or in the upper right shoulder for PET/CT imaging.
In Vivo Model A375 xenograft model
In Vitro Model Amelanotic melanoma A375 cells CVCL_0132
3G10-TG6-vc0101 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 61.00% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 1.5 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 82.80% (Day 27) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 1.5 mg/kg.
In Vivo Model HPB-ALL CDX model
In Vitro Model T acute lymphoblastic leukemia HPB-ALL cells CVCL_1820
Experiment 3 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.90% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 3 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 4 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.00% (Day 27) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 3 mg/kg.
In Vivo Model HPB-ALL CDX model
In Vitro Model T acute lymphoblastic leukemia HPB-ALL cells CVCL_1820
Experiment 5 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.00% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 6 mg/kg.
In Vivo Model HPB-ALL CDX model
In Vitro Model T acute lymphoblastic leukemia HPB-ALL cells CVCL_1820
Experiment 6 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 6 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.05 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Experiment 2 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.06 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model T acute lymphoblastic leukemia HPB-ALL cells CVCL_1820
Experiment 3 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.06 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Adult T acute lymphoblastic leukemia MOLT-4 cells CVCL_0013
Experiment 4 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.14 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma RPMI-8226 cells CVCL_0014
Experiment 5 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.86 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 6 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.53 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
6B6-TG6-vc0101 [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 67.90% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 1.5 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 85.70% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 3 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 3 Reporting the Activity Date of This ADC [9]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.00% (Day 21) Positive CXCR4 expression (CXCR4+++/++)
Method Description
Mice were treated with a single intravenous dose of the ADCs at 6 mg/kg.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Revealed Based on the Cell Line Data
Click To Hide/Show 6 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.06 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Adult T acute lymphoblastic leukemia MOLT-4 cells CVCL_0013
Experiment 2 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.07 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma MOLP-8 cells CVCL_2124
Experiment 3 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.07 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model T acute lymphoblastic leukemia HPB-ALL cells CVCL_1820
Experiment 4 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.25 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma RPMI-8226 cells CVCL_0014
Experiment 5 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.56 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Plasma cell myeloma MM1.S cells CVCL_8792
Experiment 6 Reporting the Activity Date of This ADC [9]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.00 nM
Positive CXCR4 expression (CXCR4+++/++)
Method Description
Cells were incubated with increasing concentrations of each ADCs at 37°C for 6 days in complete culture medium.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
rcEDB-ADC [Investigative]
 ADC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 69.70% (Day 18) High FN1 expression (FN1+++)
Method Description
For studies using the mouse syngeneic cell line EMT6, 8-week-old Balb/c mice were injected in the left mammary fat pad with 1 x106 cells suspended in DPBS. Tumors were measured at least twice/week. This tumor model was injected intravenously with rcEDB-ADC 9 mg/kg single.
In Vivo Model Breast cancer CDX model
In Vitro Model Mammary gland malignant neoplasms EMT6 cells CVCL_1923
Experiment 2 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 69.70% (Day 18) High FN1 expression (FN1+++)
Method Description
For studies using the mouse syngeneic cell line EMT6, 8-week-old Balb/c mice were injected in the left mammary fat pad with 1 x106 cells suspended in DPBS. Tumors were measured at least twice/week. This tumor model was injected intravenously with rcEDB-ADC 3 mg/kg q4dx3.
In Vivo Model Breast cancer CDX model
In Vitro Model Mammary gland malignant neoplasms EMT6 cells CVCL_1923
Experiment 3 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 69.70% (Day 18) High FN1 expression (FN1+++)
Method Description
For studies using the mouse syngeneic cell line EMT6, 8-week-old Balb/c mice were injected in the left mammary fat pad with 1 x106 cells suspended in DPBS. Tumors were measured at least twice/week. This tumor model was injected intravenously with rcEDB-ADC 1.5 mg/kg q4dx3.
In Vivo Model Breast cancer CDX model
In Vitro Model Mammary gland malignant neoplasms EMT6 cells CVCL_1923
Experiment 4 Reporting the Activity Date of This ADC [7]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.30% (Day 18) High FN1 expression (FN1+++)
Method Description
For studies using the mouse syngeneic cell line EMT6, 8-week-old Balb/c mice were injected in the left mammary fat pad with 1 x106 cells suspended in DPBS. Tumors were measured at least twice/week. This tumor model was injected intravenously with rcEDB-ADC 4.5 mg/kg q4dx2.
In Vivo Model Breast cancer CDX model
In Vitro Model Mammary gland malignant neoplasms EMT6 cells CVCL_1923
Anti-CXCR4 ADC 381 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.70 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-CXCR4 ADC 519 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.70 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-CXCR4 ADC 518 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
4.70 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-CXCR4 ADC 554 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.50 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-CXCR4 ADC 553 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
17.10 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-CXCR4 ADC 555 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
17.70 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
Anti-MSL1 mAb-Compound 31 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [11]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
37.38 nM
Positive MSL expression (MSL+++/++)
Method Description
The cells were incubated in a CO2 incubat or with saturated water overnight, On the second day, two covalent thiol conjugated ADCs were serially diluted conjugates were added to the 96 well plate containing OVCAR3 cells, 100uL per well. The initial conjugate was 100000 ng/ml and diluted to 0.001 ng/ml. OVCAR3 cells with added ADC were incubated at 37 for 72 hours.

   Click to Show/Hide
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Anti-CXCR4 ADC 556 [Investigative]
 ADC Info 
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [10]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
39.70 nM
High CXCR4 expression (CXCR4+++)
Method Description
Cells were seeded in a culture-treated 96-well clear plate and incubated at 37°C under 5% CO2 for 24h. Serially diluted samples (50L) were added to each well and the plate was incubated at 37°C for 72h.
In Vitro Model T acute lymphoblastic leukemia Jurkat cells CVCL_0065
PF-06664178 [Terminated in phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Objective Response Rate (ORR)
0.00%
Patients Enrolled
Advanced solid tumors resistant to standard therapy, or for which no other therapy was available, and at least one measurable lesion defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
Administration Dosage
Once every 21 days as an intravenous infusion over approximately 60 min, doses starting from 0.15 mg/kg to 6.14 mg/kg.
Related Clinical Trial
NCT Number NCT02122146  Phase Status Phase 1
Clinical Description
A phase 1, dose escalation study of Pf-06664178 in patients with locally advanced or metastatic solid tumors.
Primary Endpoint
In the 29 response-evaluable patients,the best overall response observed was limited to stable disease (SD) in 11 patients(37.90%) with PR or CR.
Other Endpoint
Doses explored ranged from 0.15 mg/kg to 4.80 mg/kg. Doses of 3.60 mg/kg,4.20 mg/kg and 4.80 mg/kg were considered intolerable due to DLTs. MTD and RP2D were not determined.
PF-06650808 [Terminated in phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [13]
Efficacy Data Objective Response Rate (ORR)
9.68% (all response-evaluable patients)
16.67% (patients with breast cancer)
21.43% (patients with ER+ breast cancer)
Patients Enrolled
Locally advanced/metastatic solid tumors resistant to standard therapy or with no available standard therapy; Eastern Cooperative Oncology Group (ECOG) performance score (PS) 01; a life expectancy 12 weeks; and adequate bone marrow, hepatic, and renal function.
Administration Dosage
Intravenously every 3 weeks (Q3W) starting at a dose of 0.20 mg/kg to be escalated up to 6.40 mg/kg, following the modified continual reassessment method (mCRM).
Related Clinical Trial
NCT Number NCT02129205  Phase Status Phase 1
Clinical Description
A phase 1 dose escalation study evaluating the safety and tolerability of PF-06650808 In patients with advanced solid tumors.
Primary Endpoint
OrR=9.68% for all response-evaluable patients (N=3/31), ORR=16.67% for patients with breast cancer (N=3/18), ORR=21.43% for patients with ER+ breast cancer (N=3/14). Five patients with advanced BC achieved PR as best overall response (BOR): 2 at 2.0 mg/kg, 1 at 2.4 mg/kg, and 2 at 3.6 mg/kg.
Other Endpoint
The maximum tolerated dose (MTD) was estimated to be 2.40 mg/kg.
Experiment 2 Reporting the Activity Date of This ADC [14]
Related Clinical Trial
NCT Number NCT02129205  Phase Status Phase 1
Clinical Description
A phase 1 dose escalation study evaluating the safety and tolerability of PF-06650808 in patients with advanced solid tumors.
References
Ref 1 Cytotoxic Barrigenol-like Triterpenoids from an Extract of Cyrilla racemiflora Housed in a Repository. J Nat Prod. 2015 Oct 23;78(10):2440-6. doi: 10.1021/acs.jnatprod.5b00532. Epub 2015 Sep 30.
Ref 2 Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer. Clin Cancer Res. 2022 Aug 2;28(15):3235-3241.
Ref 3 First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors. Clin Cancer Res. 2021 Aug 15;27(16):4511-4520.
Ref 4 A First-in-Human, Open-label, Multicenter, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Participants With Advanced Solid Tumors, NCT05720117
Ref 5 A Phase 1b Efficacy and Safety Study of Cofetuzumab Pelidotin (ABBV-647, a PTK7-Targeting Antibody Drug Conjugate) in Subjects With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer, NCT04189614
Ref 6 PF-06804103, A Site-specific Anti-HER2 Antibody-Drug Conjugate for the Treatment of HER2-expressing Breast, Gastric, and Lung Cancers. Mol Cancer Ther. 2020 Oct;19(10):2068-2078.
Ref 7 Anti-Extra Domain B Splice Variant of Fibronectin Antibody-Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade. Mol Cancer Ther. 2022 Sep 6;21(9):1462-1472.
Ref 8 Targeting and pharmacology of an anti-IL13R2 antibody and antibody-drug conjugate in a melanoma xenograft model. MAbs. 2021 Jan-Dec;13(1):1958662.
Ref 9 Anti-cxcr4 antibodies and antibody-drug conjugates.
Ref 10 Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates. Sci Rep. 2019 Feb 21;9(1):2443. doi: 10.1038/s41598-019-38745-x.
Ref 11 Covalent linkers in antibody-drug conjugates and methods of making and using the same.
Ref 12 A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors. Invest New Drugs. 2018 Oct;36(5):836-847.
Ref 13 A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors. Invest New Drugs. 2020 Feb;38(1):120-130.
Ref 14 A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS

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