ADC ID	DRG0SXFSY
ADC Name	Inotuzumab ozogamicin
Brand Name	Besponsa
Synonyms	inotuzumab ozogamicin; inotuzumab ozogamicin ; Besponsa; CMC-544; PF-5208773; inotuzumab ozogamycin; Inonza    Click to Show/Hide
Organization	Celltech (Originator) (No Rights);Wyeth (Top20 MNC)
Drug Status	Approved in 2017
Drug-to-Antibody Ratio	6
Structure
	3D MOL			2D MOL
Antibody Name	Inotuzumab					Antibody Info
Antigen Name	B-cell receptor CD22 (CD22)					Antigen Info
Payload Name	N-acetyl-gamma-calicheamicin					Payload Info
Therapeutic Target	Human deoxyribonucleic acid (hDNA)					Target Info
Linker Name	AcButDMH					Linker Info
Conjugate Type	Random Lysines
Combination Type	ozogamicin
Absorption	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks. The steady state exposure of the drug is reached by Cycle 4. The mean (SD) maximum serum concentration (Cmax) of inotuzumab ozogamicin was 308 ng/mL with patients receving the recommended dose of 1.8 mg/m2/cycle.
Distribution	The total volume of distribution of inotuzumab ozogamicin is approximately 12L. The binding of the N-acetyl-gamma-calicheamicin dimethylhydrazide to human plasma proteins to be approximately 97%.
Metabolism	N-acetyl-gamma-calicheamicin dimethylhydrazide primarily undergoes nonenzymatic reduction in vitro. The metabolism of N-acetyl-gamma-calicheamicin dimethylhydrazide in human serum is not clearly understood. The antibody portion of the drug is thought to undergo proteolytic degradation into amino acids then recycled into other proteins. The elimination half life at the end of Cycle 4 of administration is approximately 12.3 days in a 2-compartment model.
Elimination	The mean clearance rate was approximately 0.12±0.15 L/h/m2 in pediatric patients receiving a dose level of 9 mg/m2.
Toxicity	The drug is disposited in the body after administration. The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h.
Special Approval(s)	Breakthrough therapy (FDA); Orphan drug (FDA); Orphan drug (EMA)

Dissocation Constant (Kd)	Binding Target	Description	Reference
200 pM	CD22	Inotuzumab ozogamicin binds to the CD22 antigen with an affinity generally similar to that of the unconjugated G544 antibody (KD 200 and 235 pM, respectively)	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	308	ng/mL	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks.7 The mean Cmax of inotuzumab ozogamicin was 308 ng/mL	[1]
Area Under the Concentration-Time Curve (AUC)	100000	ng*h/mL	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks.7 The mean Cmax of inotuzumab ozogamicin was 308 ng/mL. The mean simulated total AUC per cycle was 100,000 ngxh/mL.    Click to Show/Hide	[1]
Maximum Observed Concentration (Cmax)	969	ng/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Maximum Observed Concentration (Cmax)	565	ng/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Area Under the Concentration-Time Curve (AUC)	14039	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Area Under the Concentration-Time Curve (AUC)	28390	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Maximum Observed Concentration (Cmax)	2.86±1.35	mg/L	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Area Under the Concentration-Time Curve (AUC)	123±105	mg*h/L	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Maximum Observed Concentration (Cmax)	191	ng/mL	1.8 Mg/m2/cycle, Pediatric R/R ALL patients, Cycle 1.	[7]
Maximum Observed Concentration (Cmax)	155	ng/mL	1.8 Mg/m2/cycle, adult R/R ALL patients, Cycle 1.	[7]
Area Under the Concentration-Time Curve (AUC)	24550	ng*h/mL	1.8 Mg/m2/cycle, Pediatric R/R ALL patients, Cycle 1.	[7]
Area Under the Concentration-Time Curve (AUC)	18200	ng*h/mL	1.8 Mg/m2/cycle, adult R/R ALL patients, Cycle 1.	[7]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	100000	ng*h/mL	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks.7 The mean Cmax of inotuzumab ozogamicin was 308 ng/mL. The mean simulated total AUC per cycle was 100,000 ngxh/mL.    Click to Show/Hide	[1]
Volume of Distribution (Vd)	12	L	In humans, the total volume of distribution of inotuzumab ozogamicin was approximately 12 L.	[1]
Area Under the Concentration-Time Curve (AUC)	14039	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Area Under the Concentration-Time Curve (AUC)	28390	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Volume of Distribution (Vd)	6.24	L	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Volume of Distribution (Vd)	5.94	L	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Volume of Distribution (Vd)	6.7	L	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, NONMEM results Volume of distribution in central compartment	[3]
Volume of Distribution (Vd)	6.69	L	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, Nonparametric bootstrap Volume of distribution in central compartment	[3]
Volume of Distribution (Vd)	5.1	L	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, NONMEM results Volume of distribution in peripheral compartment	[3]
Volume of Distribution (Vd)	4.88	L	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, Nonparametric bootstrap Volume of distribution in peripheral compartment    Click to Show/Hide	[3]
Volume of Distribution (Vd)	0.0478	L/kg	Preclinical plasma PK parameters,Volume of distribution in central compartment for ADC	[4]
Volume of Distribution (Vd)	0.0214	L/kg	Preclinical plasma PK parameters, Volume of distribution in peripheral compartment for ADC	[4]
Volume of Distribution (Vd)	0.058	L/kg	Clinical PK parameters, Volume of distribution in central compartment for ADC	[4]
Volume of Distribution (Vd)	0.0124	L/kg	Clinical PK parameters, Volume of distribution in peripheral compartment for ADC	[4]
Area Under the Concentration-Time Curve (AUC)	123±105	mg*h/L	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Volume of Distribution (Vd)	6.49	L	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Volume of distribution in central compartment NONMEM results    Click to Show/Hide	[6]
Volume of Distribution (Vd)	4.74	L	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Volume of distribution in peripheral compartment NONMEM results    Click to Show/Hide	[6]
Volume of Distribution (Vd)	6.26	L	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Volume of distribution in central compartment SIR results    Click to Show/Hide	[6]
Volume of Distribution (Vd)	3.97	L	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Volume of distribution in peripheral compartment SIR results    Click to Show/Hide	[6]
Area Under the Concentration-Time Curve (AUC)	24550	ng*h/mL	1.8 Mg/m2/cycle, Pediatric R/R ALL patients, Cycle 1.	[7]
Area Under the Concentration-Time Curve (AUC)	18200	ng*h/mL	1.8 Mg/m2/cycle, adult R/R ALL patients, Cycle 1.	[7]
Volume of Distribution (Vd)	6.56	L	1.8 Mg/m2/cycle, Central volume of distribution (V1) estimated in pediatric patients.	[7]
Volume of Distribution (Vd)	4.7	L	1.8 Mg/m2/cycle, Peripheral volume of distribution estimated in pediatric patients.	[7]
Volume of Distribution (Vd)	3.95	L	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Model results volume of distribution in central compartment	[8]
Volume of Distribution (Vd)	3.95	L	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Non-parametric bootstrap results volume of distribution in central compartment    Click to Show/Hide	[8]
Volume of Distribution (Vd)	6.18	L	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Model results volume of distribution in peripheral compartment	[8]
Volume of Distribution (Vd)	6.43	L	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Non-parametric bootstrap results volume of distribution in peripheral compartment    Click to Show/Hide	[8]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	100000	ng*h/mL	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks.7 The mean Cmax of inotuzumab ozogamicin was 308 ng/mL. The mean simulated total AUC per cycle was 100,000 ngxh/mL.    Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	14039	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Area Under the Concentration-Time Curve (AUC)	28390	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Area Under the Concentration-Time Curve (AUC)	123±105	mg*h/L	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Area Under the Concentration-Time Curve (AUC)	24550	ng*h/mL	1.8 Mg/m2/cycle, Pediatric R/R ALL patients, Cycle 1.	[7]
Area Under the Concentration-Time Curve (AUC)	18200	ng*h/mL	1.8 Mg/m2/cycle, adult R/R ALL patients, Cycle 1.	[7]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	100000	ng*h/mL	Inotuzumab ozogamicin is intended to be administered in cycles that each run for 3 to 4 weeks.7 The mean Cmax of inotuzumab ozogamicin was 308 ng/mL. The mean simulated total AUC per cycle was 100,000 ngxh/mL.    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	12.3	days	In patients with relapsed or refractory ALL, the terminal half-life was 12.3 days.	[1]
Clearance (CL)	0.0333	L/h	The pharmacokinetics of inotuzumab ozogamicin were well characterized by a 2-compartment model with linear and time-dependent clearance components. The clearance of inotuzumab ozogamicin at steady state is 0.0333 L/h in patients with relapsed or refractory ALL.    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	17.1	h	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Elimination Half-Life (t1/2)	34.7	h	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Area Under the Concentration-Time Curve (AUC)	14039	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Area Under the Concentration-Time Curve (AUC)	28390	ng*h/mL	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Clearance (CL)	0.266	L/h	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 1	[2]
Clearance (CL)	0.157	L/h	Pharmacokinetic Parameters of Inotuzumab Ozogamicin and Components After MTD Treatment by Inotuzumab Ozogamicin Treatment, Day 29	[2]
Clearance (CL)	0.113	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, NONMEM results Linear clearance	[3]
Clearance (CL)	0.114	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, Nonparametric bootstrap results Linear clearance	[3]
Clearance (CL)	0.369	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, NONMEM results Clearance associated with time-dependent clearance	[3]
Clearance (CL)	0.373	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, Nonparametric bootstrap results Clearance associated with time-dependent clearance    Click to Show/Hide	[3]
Clearance (CL)	0.0405	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, NONMEM results Intercompartment clearance	[3]
Clearance (CL)	0.0418	L/h	Population pharmacokinetics of inotuzumab ozogamicin in relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma, Nonparametric bootstrap results Intercompartment clearance	[3]
Clearance (CL)	0.039	L/day/kg	Preclinical plasma PK parameters, Plasma clearance of ADC	[4]
Clearance (CL)	0.024	L/day/kg	Preclinical plasma PK parameters, Distribution clearance of ADC	[4]
Clearance (CL)	0.029	L/day/kg	Clinical PK parameters, Plasma clearance of ADC	[4]
Clearance (CL)	0.071	L/day/kg	Clinical PK parameters, Distribution clearance of ADC	[4]
Area Under the Concentration-Time Curve (AUC)	123±105	mg*h/L	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Clearance (CL)	0.265±0.229	L/h	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Elimination Half-Life (t1/2)	72.4±42.0	h	Pharmacokinetics (PK) of Gemtuzumab Ozogamicin in AML Patients, Dose: 9 mg/m2, first dose, Administered in 59 adult AML patients in first relapse.	[5]
Clearance (CL)	0.13	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Linear clearance NONMEM results	[6]
Clearance (CL)	0.569	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Initial estimate of time-dependent clearance NONMEM results    Click to Show/Hide	[6]
Clearance (CL)	0.0437	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Intercompartment clearance NONMEM results    Click to Show/Hide	[6]
Clearance (CL)	0.12	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Linear clearance SIR results	[6]
Clearance (CL)	0.039	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Initial estimate of time-dependent clearance SIR results    Click to Show/Hide	[6]
Clearance (CL)	0.0383	L/h	Population Pharmacokinetics of Inotuzumab Ozogamicin in Pediatric Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Results of Study ITCC-059, Intercompartment clearance SIR results	[6]
Area Under the Concentration-Time Curve (AUC)	24550	ng*h/mL	1.8 Mg/m2/cycle, Pediatric R/R ALL patients, Cycle 1.	[7]
Area Under the Concentration-Time Curve (AUC)	18200	ng*h/mL	1.8 Mg/m2/cycle, adult R/R ALL patients, Cycle 1.	[7]
Clearance (CL)	0.113	L/h	1.8 Mg/m2/cycle,Linear clearance (CL1) estimated in pediatric patients.	[7]
Clearance (CL)	0.384	L/h	1.8 Mg/m2/cycle,Time-dependent clearance (CL2) estimated in pediatric patients.	[7]
Clearance (CL)	0.0532	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Model results linear clearance	[8]
Clearance (CL)	0.0515	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Non-parametric bootstrap results linear clearance	[8]
Clearance (CL)	0.506	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Model results clearance associated with time-dependent clearance	[8]
Clearance (CL)	0.507	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Non-parametric bootstrap results clearance associated with time-dependent clearance    Click to Show/Hide	[8]
Clearance (CL)	0.0248	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Model results intercompartmental clearance	[8]
Clearance (CL)	0.025	L/h	Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia, Non-parametric bootstrap results intercompartmental clearance	[8]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Partial Response (PR)	NCT01535989	Phase 1	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.
Objective Response Rate (ORR)	NCT02981628	Phase 2	Inotuzumab ozogamicin in treating younger patients with B-lymphoblastic lymphoma or relapsed or refractory CD22 positive B acute lymphoblastic leukemia.
Objective Response Rate (ORR)	NCT00073749	Phase 1	A phase 1 study of Cmc-544 administered as a single agent in subjects with B-cell non- Hodgkin's lymphoma.
Objective Response Rate (ORR)	NCT00724971	Phase 1	A phase 1 study of Cmc-544 administered in combination with rituximab in subjects with B-cell non-Hodgkin's lymphoma.
Objective Response Rate (ORR)	NCT00299494	Phase 1	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.
Objective Response Rate (ORR)	NCT00717925	Phase 1	A phase 1 study of CMC-544 administered as a single agent in subjects with B-cell non-hodgkin's lymphoma.
Complete Remission (CR)	NCT01564784	Phase 3	A study of inotuzumab ozogamicin versus investigator's choice of chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia.
Complete Remission (CR)	NCT01134575	Phase 2	Treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) with CMC-544 (Inotuzumab Ozogamycin), with or without later addition of rituximab.
Complete Remission (CR)	NCT02981628	Phase 2	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).

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 54	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 61.6	%	B-cell lymphoma cells	B-cell lymphoma
Tumor Growth Inhibition value (TGI)	≈ 68.2	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 72.8	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 72.9	%	Reh cells	B acute lymphoblastic leukemia
Tumor Growth Inhibition value (TGI)	≈ 77.1	%	Reh cells	B acute lymphoblastic leukemia
Tumor Growth Inhibition value (TGI)	≈ 79.1	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 83.6	%	Reh cells	B acute lymphoblastic leukemia
Tumor Growth Inhibition value (TGI)	≈ 88.4	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 92.2	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 93.4	%	B-cell lymphoma cells	B-cell lymphoma
Tumor Growth Inhibition value (TGI)	≈ 95.2	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 95.8	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 97.7	%	Ramos cells	Burkitt lymphoma
Tumor Growth Inhibition value (TGI)	≈ 98.3	%	B-cell lymphoma cells	B-cell lymphoma
Tumor Growth Inhibition value (TGI)	≈ 99.8	%	B-cell lymphoma cells	B-cell lymphoma

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	5	pM	Daudi cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	6	pM	RL cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	6	pM	RL cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	13	pM	Reh cells	B acute lymphoblastic leukemia
Half Maximal Inhibitory Concentration (IC50)	20	pM	Daudi cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	21	pM	Daudi cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	40	pM	Ramos cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	47	pM	RS4 11 cells	Adult B acute lymphoblastic leukemia
Half Maximal Inhibitory Concentration (IC50)	53	pM	Ramos cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	53	pM	SUP-B15 cells	B-lymphoblastic leukemia
Half Maximal Inhibitory Concentration (IC50)	80	pM	Raji cells	EBV-related Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	100	pM	Ramos cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	200	pM	Ramos cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	250	pM	HL-60 cells	Adult acute myeloid leukemia
Half Maximal Inhibitory Concentration (IC50)	300	pM	Raji cells	EBV-related Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	600	pM	RL cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	750	pM	HL-60 cells	Adult acute myeloid leukemia
Half Maximal Inhibitory Concentration (IC50)	0.02	nM	Ramos cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	0.1	nM	RL cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	0.2	nM	WSU-DLCL2 cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	0.5	nM	SU-DHL-4 cells	Diffuse large B-cell lymphoma

Experiment 1 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Partial Response (PR)	60.00, 33.00, 25.00 %	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).    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Objective Response Rate (ORR)	74%	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					[11]
Efficacy Data	Objective Response Rate (ORR)	39.24, 40.82, 68.00, 15.00 %	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.    Click to Show/Hide
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					[12]
Efficacy Data	Objective Response Rate (ORR)	80.00, 88.00 %	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.    Click to Show/Hide
Experiment 5 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Objective Response Rate (ORR)	87.00, 74.00, 20.00 %	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.    Click to Show/Hide
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).    Click to Show/Hide
Experiment 6 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Objective Response Rate (ORR)	100.00, 80.00 %	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%).    Click to Show/Hide
Experiment 7 Reporting the Activity Date of This ADC					[15]
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					[16]
Efficacy Data	Complete Remission (CR)	18%
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					[17]
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.

Experiment 1 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 54%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 61.60%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.20%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 72.80%	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					[19]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 72.90%	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					[19]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 77.10%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 79.10%	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					[19]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.60%	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					[20]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 88.40%	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					[21]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.20%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 93.40%	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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.20%	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					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.80%	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					[21]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.70%	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					[22]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.30%	Positive CD22 expression (CD22+++/++)
Method Description	CMC-544 induces efficient tumor cell killing in cell line-derived models B-cell lymphoma cell line with 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					[18]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.80%	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

Experiment 1 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5 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					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	6 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 3 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	6 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 4 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	13 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					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	20 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					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	21 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					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	40 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					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	47 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					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	53 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 10 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	53 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 11 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	80 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					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	100 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					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	200 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					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	250 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					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	300 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					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	600 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					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	750 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					[22]
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					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.1 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					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.2 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					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.5 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

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