Linker Information

General Information of This Linker
Linker ID
LIN0KWKDL
Linker Name
AcButDMH
Linker Type
pH-sensitive linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C12H15NO3
Isosmiles
CC(=O)c1ccc(OCCCC(N)=O)cc1
InChI
InChI=1S/C12H15NO3/c1-9(14)10-4-6-11(7-5-10)16-8-2-3-12(13)15/h4-7H,2-3,8H2,1H3,(H2,13,15)
InChIKey
HMGPYFKCMKBIOY-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
221.256
Polar area
69.39
Complexity
16
xlogp Value
1.5335
Heavy Count
16
Rot Bonds
6
Hbond acc
3
Hbond Donor
1
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Gemtuzumab ozogamicin [Approved]
 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 [1]
Efficacy Data Two-year Overall Survival (OS)
69.00% (standard group); 73.00% (gemtuzumab ozogamicin group)
Patients Enrolled
Eligible participants were 18 years or older and had newly diagnosed NPM1-mutated acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2.
Administration Dosage
Participants received two cycles of induction therapy plus all-trans retinoic acid (ATRA) followed by three consolidation cycles of high-dose cytarabine and ATRA, without or with gemtuzumab ozogamicin (3 mg/m2 i.v.on day 1 of induction cycles 1 and 2, and consolidation cycle 1).
Related Clinical Trial
NCT Number NCT00893399  Clinical Status Phase 3
Clinical Description
Phase III study of chemotherapy in combination with atra with or without gemtuzumab ozogamicin in patients with acute myeloid leukemia and npm1 gene mutation.
Primary Endpoint
Short-term event-free survival at 6-month follow-up, 53.00% in the standard group and 58.00% in the gemtuzumab ozogamicin group.
Other Endpoint
CRi rates, n=267 (90%) in the standard group vs n=251 (86%) in the gemtuzumab ozogamicin group.
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Objective Response Rate (ORR)
85.00%
Positive CD33 expression (CD33+++/++)
Patients Enrolled
Previously untreated primary or secondary acute myeloid leukemia (with bone marrow blasts 20%), express CD33 on blast cells.
Administration Dosage
3 mg/sqm single dose on day 6.
Related Clinical Trial
NCT Number NCT00909168  Clinical Status Phase 3
Clinical Description
Induction, consolidation and intensification therapy for patients younger than 66 years with previously untreated CD33 positive acute myeloid leukemia (AML) (MYFLAI07).
Primary Endpoint
Objective response rate=85.00%, comprising 82.00% complete responses and 3.00% partial responses.
Other Endpoint
median DFS=61 months, median OS=63 months.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 13.81% (Day 18) Positive CD33 expression (CD33+++/++)
Method Description
Subcutaneous tumor model MV4-11 human acute myelocytic leukemia cells (1x10 cells in 0.1 mL) were subcutaneously inoculated into the right flank of female athymic nude mice. Mice were treated with ADCs (iv, 0.1 mg/kg x 1) when tumors reached 150 mm3 and mouse body weight were measured twice per week.
In Vivo Model MV411 CDX model
In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
Revealed Based on the Cell Line Data
Click To Hide/Show 40 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
20.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia ML-2 cells CVCL_1418
Experiment 2 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
30.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia MOLM-13 cells CVCL_2119
Experiment 3 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
30.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Chronic eosinophilic leukemia EoL-1 cells CVCL_0258
Experiment 4 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
40.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia SKNO-1 cells CVCL_2196
Experiment 5 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
70.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Childhood acute monocytic leukemia MV4-11 cells CVCL_0064
Experiment 6 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
90.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
Experiment 7 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
90.00 pM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia OCI-AML-1 cells CVCL_5228
Experiment 8 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.10 nM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia OCI-AML-4 cells CVCL_5224
Experiment 9 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.10 nM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia AML-193 cells CVCL_1071
Experiment 10 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.10 nM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia Kasumi-6 cells CVCL_0614
Experiment 11 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Leukemia KOPN-8 cells CVCL_1866
Experiment 12 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.43 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult T acute lymphoblastic leukemia MOLT-4 cells CVCL_0013
Experiment 13 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.45 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia SKM-1 cells CVCL_0098
Experiment 14 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.52 nM
Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia HNT-34 cells CVCL_2071
Experiment 15 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.56 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult B acute lymphoblastic leukemia RS4;11 cells CVCL_0093
Experiment 16 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.58 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model B acute lymphoblastic leukemia Reh cells CVCL_1650
Experiment 17 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.47 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model B acute lymphoblastic leukemia LC4-1 cells CVCL_1374
Experiment 18 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
1.78 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model B-lymphoblastic leukemia SUP-B15 cells CVCL_0103
Experiment 19 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.57 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Childhood acute monocytic leukemia THP-1 cells CVCL_0006
Experiment 20 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
2.92 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model T acute lymphoblastic leukemia TALL-1 cells CVCL_1736
Experiment 21 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
3.31 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult T acute lymphoblastic leukemia LOUCY cells CVCL_1380
Experiment 22 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.02 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Childhood B acute lymphoblastic leukemia NALM-16 cells CVCL_1834
Experiment 23 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.03 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model T acute lymphoblastic leukemia ATN-1 cells CVCL_1073
Experiment 24 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.56 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model T acute lymphoblastic leukemia CCRF-CEM cells CVCL_0207
Experiment 25 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.61 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model T lymphoblastic lymphoma SUP-T1 cells CVCL_1714
Experiment 26 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
8.91 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Leukemia ARH-77 cells CVCL_1072
Experiment 27 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
10.20 nM
Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Leukemia Jurkat E6.1 cells CVCL_0367
Experiment 28 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Myelodysplastic syndrome F-36P cells CVCL_2037
Experiment 29 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia Kasumi-6 cells CVCL_0614
Experiment 30 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia AML-193 cells CVCL_1071
Experiment 31 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia Kasumi-3 cells CVCL_0612
Experiment 32 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Leukemia KG-1a cells CVCL_1824
Experiment 33 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute monocytic leukemia NOMO-1 cells CVCL_1609
Experiment 34 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Myeloid leukemia with maturation Kasumi-1 cells CVCL_0589
Experiment 35 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia OCI-M1 cells CVCL_2149
Experiment 36 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Positive CD33 expression (CD33+++/++)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Adult acute myeloid leukemia PLB-985 cells CVCL_2162
Experiment 37 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute megakaryoblastic leukemia CMK-11-5 cells CVCL_0217
Experiment 38 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Chronic myeloid leukemia KU812 cells CVCL_0379
Experiment 39 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute erythroid leukemia TF-1a cells CVCL_3608
Experiment 40 Reporting the Activity Date of This ADC [12]
Efficacy Data Half Maximal Inhibitory Concentration (IC50) > 20.00 nM Negative CD33 expression (CD33-)
Method Description
The cells, at a predetermined concentration, were plated into 96 well plates, and, after overnight incubation at 37°C/5% CO2, serial dilutions of each test article (TA) were added to the cells. Cells were incubated with test articles for 72 hours. and viability was detected with CellTiter-Gloreagent.
In Vitro Model Acute myeloid leukemia GDM-1 cells CVCL_1230
Inotuzumab ozogamicin [Approved]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 9 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Efficacy Data Partial Response (PR)
60.00% (DL2a)
33.00% (DL1a)
25.00% (DL1)
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas.
Administration Dosage
InO 0.80 mg/m2 on d1 and TEM 15 mg d1,8,15,22 q28d (of the four patients included in dose level (DL) 1 ); InO 0.80 mg/m2 on d1 and TEM 10 mg d1,8,15,22 q28d (DL-1) w.
Related Clinical Trial
NCT Number NCT01535989  Clinical Status Phase 1
Clinical Description
A phase 1 study of inotuzumab ozogamicin (CMC-544) in combination with temsirolimus (CCI-779) in patients with relapsed or refractory CD22-positive B-cell non Hodgkin's lymphomas.
Primary Endpoint
Anti-tumor activity was observed in three of the four dose levels tested (PR 60.00% in DL2a, 33.00% in DL1a, and 25.00% in DL1).
Other Endpoint
Patients received a total of 47 cycles of study treatment with a median of two cycles (range 16). Of the four patients included in dose level (DL) 1 (InO 0.80 mg/m2 on d1 and TEM 15 mg d1, 8, 15, 22 q28d), two patients experienced DLTs (grade 4 thrombocytopenia and inability to receive 75% planned dose of TEM in one patient and grade 3 hypertriglyceridemia in another) and DL-1 (InO 0.80 mg/m2 on d1 and TEM 10 mg d1, 8, 15, 22 q28d) was evaluated again with the occurrence of DLTs in the first treated patient (grade 3 general physical health deterioration and inability to receive at least 3/4 doses of TEM).

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Experiment 2 Reporting the Activity Date of This ADC [4]
Efficacy Data Objective Response Rate (ORR)
74.00%
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Patients were eligible if they were 21 years of age at the time of InO administration and had received a minimum of one dose of InO.
Administration Dosage
One cycle consisted of three doses: 0.8 mg/m2 on week 1 followed by 0.5 mg/m2 on weeks 2 and 3.
Related Clinical Trial
NCT Number NCT02981628  Clinical Status Phase 2
Clinical Description
Inotuzumab ozogamicin in treating younger patients with B-lymphoblastic lymphoma or relapsed or refractory CD22 positive B acute lymphoblastic leukemia.
Primary Endpoint
Complete responses were reported in 28 of 42 (66.67%) patients with overt relapse (M2/M3 marrow): CR in 15 (35.71%) and CRi in 13 (30.95%).
Other Endpoint
Three patients had a partial response (7.14%) and eight had no response (19.05%).
Experiment 3 Reporting the Activity Date of This ADC [5]
Efficacy Data Objective Response Rate (ORR)
39.24% (all 79 patients)
40.82% (for the 49 patients treated at the MTD)
68.00% (for patients with FL)
15.00% (for patients with DLBCL)
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Relapsed or refractory CD22+ B-cell non-Hodgkin's lymphoma (NHL).
Administration Dosage
Once every 3 or 4 weeks at doses ranging from 0.40 to 2.40 mg/m2.
Related Clinical Trial
NCT Number NCT00073749  Clinical Status Phase 1
Clinical Description
A phase 1 study of Cmc-544 administered as a single agent in subjects with B-cell non- Hodgkin's lymphoma.
Primary Endpoint
Among all 79 patients across all doses, the ORR at the end of treatment was 39.24%. For the 49 patients treated at the MTD, the ORR was 40.82% (95% CI, 27.00% to 56.00%). For patients with FL, ORR was 68.00% (95% CI, 45.00% to 86.00%); for patients with DLBCL, ORR was 15.00% (95% CI, 4.00% to 35.00%). For the 43 patients enrolled onto the expanded MTD cohort, duration of response ranged from 63 to 644 days for patients with FL (n=18) and from 34 to 685 days for patients with DLBCL (n=25). Median PFS was 317 days (95% CI, 112 to 575 days) for patients with FL and 49 days (95% CI, 28 to 105 days) for patients with DLBCL. Median OS was 193 days (95% CI, 103 to 362 days) for patients with DLBCL.

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Other Endpoint
The MTD was declared to be 1.80 mg/m2. DLTs also occurred at 1.34 and 1.80 mg/m2 but did not meet criteria for escalation stop.
Experiment 4 Reporting the Activity Date of This ADC [6]
Efficacy Data Objective Response Rate (ORR)
80.00% (In the ITT population)
88.00% (In the eight evaluable patients who received two or more cycles of study treatment and had one or more post-baseline tumor assessment)
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Relapsed or refractory B-cell non-Hodgkin lymphoma.
Administration Dosage
A fixed standard dose of rituximab 375 mg/m2 was administered i.v. on day 1 of a 28-day (2 days) cycle followed by inotuzumab ozogamicin 1.80 mg/m2 i.v. on day 2 of the cycle.
Related Clinical Trial
NCT Number NCT00724971  Clinical Status Phase 1
Clinical Description
A phase 1 study of Cmc-544 administered in combination with rituximab in subjects with B-cell non-Hodgkin's lymphoma.
Primary Endpoint
Os at 1 year (52 weeks) was 100.00%, as no deaths were observed during the study. In the ITT population, the ORR was 80.00% (95% CI, 44.00-98.00%). In the eight evaluable patients who received two or more cycles of study treatment and had one or more post-baseline tumor assessment, ORR was 88.00% (95% CI, 47.00-99.00%). The duration of response ranged from 346 to 540 days. In the ITT population, the best overall responses (from the start of treat-ment until PD) were CR in six patients. In the evaluable population, CR was achieved in six patients and CRu and SD were achieved in one patient each. The PFS rate at 1 year was 89.00% (95% CI, 43-98%) in the ITT population and 88.00% (95% CI, 39-98%) in the evaluable population.

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Experiment 5 Reporting the Activity Date of This ADC [7]
Efficacy Data Objective Response Rate (ORR)
87.00% (FL)
74.00% (DLBCL)
20.00% (andrefractory disease)
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL (eligible subtypes: DLBCL, transformed FL, follicular grade 3b, or mantle cells). Refractory was defined as disease progression less than 6 months from the start of the most recent rituximab-containing treatment.
Administration Dosage
Five patients received INO 0.80 mg/m2, three received INO 1.30 mg/m2, and seven received INO 1.80 mg/m2 in combination with rituximab at 375 mg/m2 once every 4 weeksm2.
Related Clinical Trial
NCT Number NCT00299494  Clinical Status Phase 1
Clinical Description
A phase 1/2 study Of Cmc-544 administered in combination with rituximab in subjects with follicular or diffuse large B-cell non-Hodgkin's lymphoma.
Primary Endpoint
At MTD treatment, objective response rate (ORR) was 87.00%, 74.00%, and 20.00% for patients with FL, DLBCL, andrefractory disease, respectively. Confirmed complete response (CR) and unconfirmed CR were achieved in 62.00% of patients with FL and 50.00% of patients with relapsed DLBCL. Median duration of response was 17.70 months for relapsed DLBCL, 6.10 months for refractory aggressive NHL.

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Other Endpoint
For FL group, one-year PFS rate was 87.00%; two-year PFS rate was 68.00%. For relapsed FL group, one-year OS rate was 97.00%; two-year OS rate was 90.00%. For relapsed DLBCL group, one-year PFS rate was 55.00%, one-year OS rate was 80.00%; two-year PFS rate was 42.00%, two-year OS rate was 69.00%, median PFS was 17.10 months. In total, 36.00% of patients with refractory disease were alive at 2 years (median OS, 8.80 months).

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Experiment 6 Reporting the Activity Date of This ADC [8]
Efficacy Data Objective Response Rate (ORR)
100.00% (In the 1.3 mg m2 cohort)
80.00% (In the 1.8 mg m2 cohort)
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Relapsed or refractory CD22-positive B-NHL without major organ dysfunction.
Administration Dosage
1.30 mg/m2 administered IV once every 28 days, and dose escalation was performed up to the MTD of 1.80 mg/m2 administered IV once every 28 days.
Related Clinical Trial
NCT Number NCT00717925  Clinical Status Phase 1
Clinical Description
A phase 1 study of CMC-544 administered as a single agent in subjects with B-cell non-hodgkin's lymphoma.
Primary Endpoint
Antitumor activity was observed at both dose levels. In the 1.30 mg/m2 cohort, two out of three patients had CR, and one patient had CRu for an ORR of 100.00% (95% CI, 29.00-100.00%). In the 1.80 mg/m2 cohort, one out of 10 patients had CR, three patients had CRu, and four patients had PR for an ORR of 80.00% (95% CI, 44.00-98.00%).

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Experiment 7 Reporting the Activity Date of This ADC [9]
Efficacy Data Complete Remission (CR)
73.80%
Positive CD22 expression (CD22+++/++)
Patients Enrolled
Eligible patients were 18 years old, had a diagnosis of R/R CD22 positive BCP ALL.
Administration Dosage
307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm).
Related Clinical Trial
NCT Number NCT01564784  Clinical Status Phase 3
Clinical Description
A study of inotuzumab ozogamicin versus investigator's choice of chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia.
Primary Endpoint
The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC, with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2 year OS rates of 22.80% and 10.00%, respectively.
Other Endpoint
More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any followup induction therapy (39.60%vs10.50%).
Experiment 8 Reporting the Activity Date of This ADC [10]
Efficacy Data Complete Remission (CR)
18.00%
Patients Enrolled
Refractory and relapsed acute lymphocytic leukemia (ALL).
Administration Dosage
1.80 mg/m2 inotuzumab ozogamicin intravenously over 1 h every 34 weeks.
Related Clinical Trial
NCT Number NCT01134575  Clinical Status Phase 2
Clinical Description
Treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) with CMC-544 (Inotuzumab Ozogamycin), with or without later addition of rituximab.
Primary Endpoint
Median overall survival was 5.10 months (95% CI 3.80-6.40). Median survival for the 28 responders was 7.90 months (95% CI 5.30-10.50). Among the nine patients with complete response, the estimated survival at 12 months was 78.00%.
Other Endpoint
Among the 19 patients with marrow responses but no platelet or incomplete blood cell count recovery, the median survival was 6.70 months (95% CI 3.90-9.50), and among the remaining 21 patients it was 2.40 months (1.70-3.90).
Experiment 9 Reporting the Activity Date of This ADC [11]
Efficacy Data Complete Remission (CR)
39.60%
Patients Enrolled
R/R CD22-positive B-acute lymphocytic leukemia(ALL).
Administration Dosage
0.80 mg/m2 intravenously on day 1 and 0.50 mg/m2 on days 8 and 15 of a 28-day cycle.
Related Clinical Trial
NCT Number NCT02981628  Clinical Status Phase 2
Clinical Description
A phase 2 study of inotuzumab ozogamicin (NSC# 772518) in children and young adults with relapsed or refractory CD22+ B-acute lymphoblastic leukemia (B-ALL).
Primary Endpoint
Cr=39.60%, CRi=18.80% in cycle 1; CR and CRi=62.50% in cycle 2.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 16 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 54.00% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a Ramos BCL with CD22+, administered intraperitoneally as 3 doses, 1 every 4 days at 10 ug/kg.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 2 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 61.60% (Day 24) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a small RL BCL with CD22+, administered as 3 doses, 1 every 4 days via either the intraperitoneal or intravenous route at 20 ug/kg.
In Vivo Model RL BCL cell line xenograft model
In Vitro Model B-cell lymphoma B-cell lymphoma cells Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 68.20% (Day 14) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a developing Ramos BCL with CD22+, administered intraperitoneally as 3 doses, 1 every 4 days at 160 ug/kg.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 4 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 72.80% (Day 14) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of large Ramos BCL ((almost 10% of the body weight) with CD22+, administered intraperitoneally as 3 doses, 1 every 4 days at 160 ug/kg.
In Vivo Model Large ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 72.90% (Day 45) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-ALL of cells with CD22+, dosed weekly at 10 ug/kg ip Q4D3.
In Vivo Model REH B-ALL cell line xenograft model
In Vitro Model B acute lymphoblastic leukemia Reh cells CVCL_1650
Experiment 6 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 77.10% (Day 45) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-ALL of cells with CD22+, dosed weekly at 40 ug/kg ip Q4D3.
In Vivo Model REH B-ALL cell line xenograft model
In Vitro Model B acute lymphoblastic leukemia Reh cells CVCL_1650
Experiment 7 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 79.10% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a Ramos BCL with CD22+, administered intraperitoneally as 3 doses, 1 every 4 days at 40 ug/kg.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 8 Reporting the Activity Date of This ADC [14]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 83.60% (Day 45) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-ALL of cells with CD22+, dosed weekly at 160 ug/kg ip Q4D3.
In Vivo Model REH B-ALL cell line xenograft model
In Vitro Model B acute lymphoblastic leukemia Reh cells CVCL_1650
Experiment 9 Reporting the Activity Date of This ADC [15]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 88.40% (Day 9) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX models of an s.c. B-cell lymphoma, dosed at 160 ug/kg, i.p., q4d3 to scid mice with s.c. Ramos B-cell lymphoma xenografts.
In Vivo Model Ramos CDX model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 10 Reporting the Activity Date of This ADC [16]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 92.20% (Day 30) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-cell lymphoma cell line with CD22+, dosed weekly at 16 ug/kg ip Q4D3.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 11 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 93.40% (Day 24) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a small RL BCL with CD22+, administered as 3 doses, 1 every 4 days via either the intraperitoneal or intravenous route at 80 ug/kg.
In Vivo Model RL BCL cell line xenograft model
In Vitro Model B-cell lymphoma B-cell lymphoma cells Homo sapiens
Experiment 12 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.20% (Day 12) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a Ramos BCL with CD22+, administered intraperitoneally as 3 doses, 1 every 4 days at 160 ug/kg.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 13 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 95.80% (Day 35) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-cell lymphoma cell line with CD22+, dosed at ip 80 ug/kg Q4Dx3.
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 14 Reporting the Activity Date of This ADC [16]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 97.70% (Day 30) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 and rituximab combination induces efficient tumor cell killing in cell line-derived models B-cell lymphoma cell line with CD22+, dosed ip CMC-544 (16 ug/kg Q4D3) and Rituximab (2 mg/kg Q4D3).
In Vivo Model Ramos BCL cell line xenograft model
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 15 Reporting the Activity Date of This ADC [17]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 98.30% (Day 35) Positive CD22 expression (CD22+++/++)
Method Description
CMC-544 induces efficient tumor cell killing in cell line-derived models B-cell lymphoma cell line with lower CD22 expression, dosed at ip 160 ug/kg Q4Dx3.
In Vivo Model RL BCL cell line xenograft model
In Vitro Model B-cell lymphoma B-cell lymphoma cells Homo sapiens
Experiment 16 Reporting the Activity Date of This ADC [13]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.80% (Day 24) Positive CD22 expression (CD22+++/++)
Method Description
Inotuzumab ozogamicin induces efficient tumor cell killing in CDX model of a small RL BCL with CD22+, administered as 3 doses, 1 every 4 days via either the intraperitoneal or intravenous route at 320 ug/kg.
In Vivo Model RL BCL cell line xenograft model
In Vitro Model B-cell lymphoma B-cell lymphoma cells Homo sapiens
Revealed Based on the Cell Line Data
Click To Hide/Show 21 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [16]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
5.00 pM
Method Description
The inhibitory activity of CMC-544 combining with rituximab against cancer cell growth was evaluated in various BCL cell lines in vitro. The cell was cultured for 4 days with increasing concentrations of CMC-544 in the presence of 20 ug/mL of rituximab.
In Vitro Model Burkitt lymphoma Daudi cells CVCL_0008
Experiment 2 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
6.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
Human B-lymphoma cells were cultured for 96 hours in the presence of various concentrations of CMC-544, CMA-676, or unconjugated CalichDMH after which the viable cell number in each culture was enumerated by their exclusion of propidium iodide and detected by flow cytometry.
In Vitro Model Diffuse large B-cell lymphoma RL cells CVCL_1660
Experiment 3 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
6.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model Diffuse large B-cell lymphoma RL cells CVCL_1660
Experiment 4 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
13.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model B acute lymphoblastic leukemia Reh cells CVCL_1650
Experiment 5 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
20.00 pM
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model Burkitt lymphoma Daudi cells CVCL_0008
Experiment 6 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
21.00 pM
Method Description
Human B-lymphoma cells were cultured for 96 hours in the presence of various concentrations of CMC-544, CMA-676, or unconjugated CalichDMH after which the viable cell number in each culture was enumerated by their exclusion of propidium iodide and detected by flow cytometry.
In Vitro Model Burkitt lymphoma Daudi cells CVCL_0008
Experiment 7 Reporting the Activity Date of This ADC [16]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
40.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 combining with rituximab against cancer cell growth was evaluated in various BCL cell lines in vitro. The cell was cultured for 4 days with increasing concentrations of CMC-544 in the presence of 100 ug/mL of rituximab.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 8 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
47.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model Adult B acute lymphoblastic leukemia RS4;11 cells CVCL_0093
Experiment 9 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
53.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model B-lymphoblastic leukemia SUP-B15 cells CVCL_0103
Experiment 10 Reporting the Activity Date of This ADC [16]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
53.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 combining with rituximab against cancer cell growth was evaluated in various BCL cell lines in vitro. The cell was cultured for 4 days with increasing concentrations of CMC-544 in the presence of 20 ug/mL of rituximab.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 11 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
80.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
Experiment 12 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
100.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 13 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
200.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
Human B-lymphoma cells were cultured for 96 hours in the presence of various concentrations of CMC-544, CMA-676, or unconjugated CalichDMH after which the viable cell number in each culture was enumerated by their exclusion of propidium iodide and detected by flow cytometry.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 14 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
250.00 pM
Method Description
Human B-lymphoma cells were cultured for 96 hours in the presence of various concentrations of CMC-544, CMA-676, or unconjugated CalichDMH after which the viable cell number in each culture was enumerated by their exclusion of propidium iodide and detected by flow cytometry.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
Experiment 15 Reporting the Activity Date of This ADC [13]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
300.00 pM
Negative CD22 expression (CD22-); Positive CD33 expression (CD33+++/++)
Method Description
Human B-lymphoma cells were cultured for 96 hours in the presence of various concentrations of CMC-544, CMA-676, or unconjugated CalichDMH after which the viable cell number in each culture was enumerated by their exclusion of propidium iodide and detected by flow cytometry.
In Vitro Model EBV-related Burkitt lymphoma Raji cells CVCL_0511
Experiment 16 Reporting the Activity Date of This ADC [16]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
600.00 pM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 combining with rituximab against cancer cell growth was evaluated in various BCL cell lines in vitro. The cell was cultured for 4 days with increasing concentrations of CMC-544 in the presence of 20 ug/mL of rituximab.
In Vitro Model Diffuse large B-cell lymphoma RL cells CVCL_1660
Experiment 17 Reporting the Activity Date of This ADC [14]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
750.00 pM
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various ALL or B-NHL cell lines in vitro. The cell was examined in 96h in vitro culture assays.
In Vitro Model Adult acute myeloid leukemia HL-60 cells CVCL_0002
Experiment 18 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.02 nM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various B-lymphoma cell lines in vitro. BCL cells were cultured in the presence of increasing concentrations of drugs and, after 96 h, the number of surviving live cells in culture was enumerated using the MTS assay.
In Vitro Model Burkitt lymphoma Ramos cells CVCL_0597
Experiment 19 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.10 nM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various B-lymphoma cell lines in vitro. BCL cells were cultured in the presence of increasing concentrations of drugs and, after 96 h, the number of surviving live cells in culture was enumerated using the MTS assay.
In Vitro Model Diffuse large B-cell lymphoma RL cells CVCL_1660
Experiment 20 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.20 nM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various B-lymphoma cell lines in vitro. BCL cells were cultured in the presence of increasing concentrations of drugs and, after 96 h, the number of surviving live cells in culture was enumerated using the MTS assay.
In Vitro Model Diffuse large B-cell lymphoma WSU-DLCL2 cells CVCL_1902
Experiment 21 Reporting the Activity Date of This ADC [17]
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
0.50 nM
Positive CD22 expression (CD22+++/++)
Method Description
The inhibitory activity of CMC-544 against cancer cell growth was evaluated in various B-lymphoma cell lines in vitro. BCL cells were cultured in the presence of increasing concentrations of drugs and, after 96 h, the number of surviving live cells in culture was enumerated using the MTS assay.
In Vitro Model Diffuse large B-cell lymphoma SU-DHL-4 cells CVCL_0539
PF-06647263 [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 [18]
Efficacy Data Objective Response Rate (ORR)
10.40% (all dose-escalation groups)
9.10% (in the 0.015 mg/kg QW group )
Patients Enrolled
Advanced solid tumors resistant to standard therapy or for which no standard therapy.
Administration Dosage
Every 3 weeks (Q3W) or every week (QW), following a modified toxicity probability interval (mTPI) method (initial dosing: 0.015 mg/kg Q3W).
Related Clinical Trial
NCT Number NCT02078752  Clinical Status Phase 1
Clinical Description
A first-in-human phase 1, dose escalation, safety and pharmacokinetic study of PF-06647263 in adult patients with advanced solid tumors.
Primary Endpoint
Six (10.00%) patients achieved a confirmed partial response and 22 (36.70%) patients had stable disease. No correlations were observed between tumor responses and EFNA4 expression levels. Study findings showed manageable safety and favorable PK for PF-06647263 administered QW at the RP2D,with preliminary evidence of limited antitumor activity in patients with TNBC and ovarian cancer.

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Other Endpoint
The RP2D was determined to be 0.015 mg/kg QW.
Experiment 2 Reporting the Activity Date of This ADC [20]
Related Clinical Trial
NCT Number NCT02078752  Clinical Status Phase 1
Clinical Description
A first-in-human phase 1, dose escalation, safety and pharmacokinetic study of PF-06647263 in adult patients with advanced solid tumors.
CMD-193 [Terminated in 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 [19]
Efficacy Data Complete Remission (CR)
0.00%
Patients Enrolled
Patients with advanced tumours expressing the Lewis-Y antigen.
Administration Dosage
111-In-CMD-193 iv then 1.00 mg/m^2, 2.60 mg/m^2 iv of CMD-193.
Related Clinical Trial
NCT Number NCT00293215  Clinical Status Phase 1
Clinical Description
Biodistribution study of cmd-193 in patients with advanced tumours expressing the LEWIS-Y antigen.
Experiment 2 Reporting the Activity Date of This ADC [21]
Patients Enrolled
Patients with advanced malignant tumors.
Administration Dosage
CMD-193 iv.
Related Clinical Trial
NCT Number NCT00257881  Clinical Status Phase 1
Clinical Description
Phase 1 biodistribution study of 111-indium-CMD-193 in patients with advanced tumours expressing the LEWIS-Y antigen.
Experiment 3 Reporting the Activity Date of This ADC [22]
Patients Enrolled
Patients with advanced malignant tumors.
Administration Dosage
CMD-193 iv.
Related Clinical Trial
NCT Number NCT00161642  Clinical Status Phase 1
Clinical Description
Phase 1 dose-escalation study of intravenous CMD-193 in subjects with advanced malignant solid tumors.
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 [23]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 99.00% (Day 100) Positive Lewis-Y expression (Lewis-Y +++/++)
Method Description
hu3S193-CalichDMH (4 ug) induces efficient tumor cell killing in cell line-derived models of PV-1 cells with CD28 expression.
In Vivo Model N193 CDX model
In Vitro Model Gastric tubular adenocarcinoma NCI-N87 cells CVCL_1603
References
Ref 1 Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09-09): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2023 Jul;10(7):e495-e509. doi: 10.1016/S2352-3026(23)00089-3. Epub 2023 May 12.
Ref 2 A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas. Leuk Lymphoma. 2022 Jan;63(1):117-123.
Ref 3 Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial. Am J Hematol. 2018 May;93(5):655-663. doi: 10.1002/ajh.25057. Epub 2018 Mar 2.
Ref 4 Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2019 Apr;33(4):884-892. doi: 10.1038/s41375-018-0265-z. Epub 2018 Sep 28.
Ref 5 Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol. 2010 Apr 20;28(12):2085-93.
Ref 6 Phase I study of anti-CD22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Sci. 2012 May;103(5):933-8.
Ref 7 Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83.
Ref 8 Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy. Cancer Sci. 2010 Aug;101(8):1840-5.
Ref 9 Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019 Jul 15;125(14):2474-2487. doi: 10.1002/cncr.32116. Epub 2019 Mar 28.
Ref 10 Expression of concern: "Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained primary infertility: a prospective analysis of 88 cases" [Eur J Obstet Gynecol Reprod Biol. 2011 Mar;155(1):54-7. doi: 10.1016/j.ejogrb.2010.11.015. Epub 2010 Dec 23. PMID: 21185112]. Eur J Obstet Gynecol Reprod Biol. 2023 Jun;285:186.
Ref 11 Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621. J Clin Oncol. 2022 Mar 20;40(9):956-967.
Ref 12 Neodegrader conjugates; 2021-10-07.
Ref 13 Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004 Mar 1;103(5):1807-14.
Ref 14 Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia. 2007 Nov;21(11):2240-5.
Ref 15 Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin Cancer Res. 2004 Dec 15;10(24):8620-9.
Ref 16 Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin's B-cell lymphoma. Clin Cancer Res. 2006 Jan 1;12(1):242-9.
Ref 17 Preclinical anti-tumor activity of antibody-targeted chemotherapy with CMC-544 (inotuzumab ozogamicin), a CD22-specific immunoconjugate of calicheamicin, compared with non-targeted combination chemotherapy with CVP or CHOP. Cancer Chemother Pharmacol. 2011 Apr;67(4):741-9.
Ref 18 First-in-human, phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody-drug conjugate, in patients with advanced solid tumors. Int J Cancer. 2019 Oct 1;145(7):1798-1808.
Ref 19 Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
Ref 20 A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Ref 21 Phase 1 Dose-Escalation Study of Intravenous CMD-193 in Subjects With Advanced Malignant Solid Tumors
Ref 22 A Phase 1 Dose Escalation Study of CMD-193 in Subjects With Advanced Malignant Tumors.
Ref 23 Antibody-targeted chemotherapy with the calicheamicin conjugate hu3S193-N-acetyl gamma calicheamicin dimethyl hydrazide targets Lewisy and eliminates Lewisy-positive human carcinoma cells and xenografts. Clin Cancer Res. 2004 Jul 1;10(13):4538-49. doi: 10.1158/1078-0432.CCR-04-0037.

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