ADC ID	DRG0MHAHZ
ADC Name	Coltuximab ravtansine
Synonyms	coltuximab ravtansine; SAR3419; anti-CD19-SPDB-DM4    Click to Show/Hide
Organization	ImmunoGen (Top20 MNC) (Originator);Sanofi (Top20 MNC) (No Rights)
Drug Status	Phase 2 (discontinued)
Drug-to-Antibody Ratio	3 to 4 (3.5)
Structure
				2D MOL
Antibody Name	Coltuximab					Antibody Info
Antigen Name	B-lymphocyte antigen CD19 (CD19)					Antigen Info
Payload Name	DM4					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	N-succinimidyl 4-(2-pyridyldithio) butanoate (SPDB)					Linker Info
Conjugate Type	Random Lysines
Combination Type	ravtansine

Bystander Killing Effect	Description	Reference
yes	The target and nontarget cells were mixed at different ratios and treated either with SAR3419 or with the huB4-SMCC-DM1 conjugate at a concentration of 7.5 nM. While both conjugates killed the Farage cells equally well, and neither killed monocultures of HL60 cells at this concentration, the noncleavable huB4-SMCC-DM1 conjugate showed no capacity for bystander killing of the HL60 cells, while the SAR3419 was able to eradicate the HL60 cells as well as Farage cells in the mixed cell culture    Click to Show/Hide	[4]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	32.4	ug/mL	First administration (cycle 1, week 1), he maximum plasma concentration was delayed following the end of the 1-h infusion.	[1]
Maximum Observed Concentration (Cmax)	32.4	ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1)	[1]
Time to Maximum Concentration (Tmax)	0.14	day	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1)	[1]
Area Under the Concentration-Time Curve (AUC)	110	day*ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1), AUC0-7d.	[1]
Maximum Observed Concentration (Cmax)	47	ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Time to Maximum Concentration (Tmax)	0.12	day	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Area Under the Concentration-Time Curve (AUC)	292	day*ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12), AUC0-14d.	[1]
Maximum Observed Concentration (Cmax)	28.4	ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after first administration, weekly optimized N=40.	[2]
Area Under the Concentration-Time Curve (AUC)	103	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after first administration, weekly optimized N=40.	[2]
Maximum Observed Concentration (Cmax)	50.5	ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	227	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Maximum Observed Concentration (Cmax)	41.6	ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	260	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Maximum Observed Concentration (Cmax)	4.09	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 10 mg/m2, n=1.	[3]
Maximum Observed Concentration (Cmax)	7.77	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 20 mg/m2, n=3.	[3]
Maximum Observed Concentration (Cmax)	16.5	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 40 mg/m2, n=3.	[3]
Maximum Observed Concentration (Cmax)	42.5	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 80 mg/m2, n=3.	[3]
Maximum Observed Concentration (Cmax)	95.4	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 160 mg/m2, n=19.	[3]
Maximum Observed Concentration (Cmax)	95.4	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 208 mg/m2, n=6.	[3]
Maximum Observed Concentration (Cmax)	107	ug/mL	Mean and CV% for SAR3419 on Cycle 1, 270 mg/m2, n=2.	[3]
Area Under the Concentration-Time Curve (AUC)	27	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 10 mg/m2, n=1.	[3]
Area Under the Concentration-Time Curve (AUC)	35.8	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 20 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	59	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 40 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	266	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 80 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	720	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 160 mg/m2, n=19.	[3]
Area Under the Concentration-Time Curve (AUC)	738	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 208 mg/m2, n=6.	[3]
Area Under the Concentration-Time Curve (AUC)	736	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 270 mg/m2, n=2.	[3]

Standard Type	Value	Units	Description	Reference
Volume of Distribution (Vd)	3.62	L	First administration (cycle 1, week 1), Its PK was characterized by low clearance (0·340 l/d) and volume of distribution (3·62 l), associated with a long terminal half-life (t1/2z) (8·39 d).    Click to Show/Hide	[1]
End-of-Infusion Concentration (Ceoi)	27.2	ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1)	[1]
Area Under the Concentration-Time Curve (AUC)	110	day*ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1), AUC0-7d.	[1]
End-of-Infusion Concentration (Ceoi)	41.8	ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Area Under the Concentration-Time Curve (AUC)	292	day*ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12), AUC0-14d.	[1]
Volume of Distribution (Vd)	3.62	L	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Area Under the Concentration-Time Curve (AUC)	103	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after first administration, weekly optimized N=40.	[2]
Area Under the Concentration-Time Curve (AUC)	227	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Volume of Distribution (Vd)	6.39	L	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	260	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Volume of Distribution (Vd)	4.34	L	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	27	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 10 mg/m2, n=1.	[3]
Area Under the Concentration-Time Curve (AUC)	35.8	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 20 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	59	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 40 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	266	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 80 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	720	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 160 mg/m2, n=19.	[3]
Area Under the Concentration-Time Curve (AUC)	738	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 208 mg/m2, n=6.	[3]
Area Under the Concentration-Time Curve (AUC)	736	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 270 mg/m2, n=2.	[3]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	110	day*ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1), AUC0-7d.	[1]
Area Under the Concentration-Time Curve (AUC)	292	day*ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12), AUC0-14d.	[1]
Area Under the Concentration-Time Curve (AUC)	103	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after first administration, weekly optimized N=40.	[2]
Area Under the Concentration-Time Curve (AUC)	227	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	260	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	27	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 10 mg/m2, n=1.	[3]
Area Under the Concentration-Time Curve (AUC)	35.8	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 20 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	59	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 40 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	266	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 80 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	720	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 160 mg/m2, n=19.	[3]
Area Under the Concentration-Time Curve (AUC)	738	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 208 mg/m2, n=6.	[3]
Area Under the Concentration-Time Curve (AUC)	736	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 270 mg/m2, n=2.	[3]

Standard Type	Value	Units	Description	Reference
Clearance (CL)	0.34	L/day	First administration (cycle 1, week 1), Its PK was characterized by low clearance (0·340 l/d) and volume of distribution (3·62 l), associated with a long terminal half-life (t1/2z) (8·39 d).    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	8.39	days	First administration (cycle 1, week 1), Its PK was characterized by low clearance (0·340 l/d) and volume of distribution (3·62 l), associated with a long terminal half-life (t1/2z) (8·39 d).    Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	110	day*ug/mL	Coltuximab ravtansine pk parameters after first administration (cycle 1, week 1), AUC0-7d.	[1]
Area Under the Concentration-Time Curve (AUC)	292	day*ug/mL	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12), AUC0-14d.	[1]
Elimination Half-Life (t1/2)	8.39	day	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Clearance (CL)	0.34	L/day	Coltuximab ravtansine pk parameters after last administration (cycle 3, week 12)	[1]
Area Under the Concentration-Time Curve (AUC)	103	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after first administration, weekly optimized N=40.	[2]
Area Under the Concentration-Time Curve (AUC)	227	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Elimination Half-Life (t1/2)	8.96	day	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Clearance (CL)	0.514	L/day	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, weekly N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	260	day*ug/mL	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Elimination Half-Life (t1/2)	7.99	day	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Clearance (CL)	0.438	L/day	PK parameters of SAR3419 at 55 mg/m2 obtained after last administration, optimized N=14.	[2]
Area Under the Concentration-Time Curve (AUC)	27	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 10 mg/m2, n=1.	[3]
Area Under the Concentration-Time Curve (AUC)	35.8	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 20 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	59	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 40 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	266	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 80 mg/m2, n=3.	[3]
Area Under the Concentration-Time Curve (AUC)	720	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 160 mg/m2, n=19.	[3]
Area Under the Concentration-Time Curve (AUC)	738	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 208 mg/m2, n=6.	[3]
Area Under the Concentration-Time Curve (AUC)	736	day*ug/mL	Mean and CV% for SAR3419 on Cycle 1, 270 mg/m2, n=2.	[3]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
stable disease (SD)	NCT01472887	PHASE2	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma    Click to Show/Hide
stable disease (SD)	NCT00796731	PHASE1	A Dose-escalation, Safety and Pharmacokinetic Study of SAR3419 Administered as a Single Agent by Intravenous Infusion Once Weekly in Patients With Relapsed/Refractory CD19-positive B-cell Non-Hodgkin's Lymphoma (NHL)    Click to Show/Hide
progressive disease (PD)	NCT01472887	PHASE2	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma    Click to Show/Hide
Partial Response (PR)	NCT01472887	PHASE2	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma    Click to Show/Hide
Objective Response Rate (ORR)	NCT01440179	PHASE2	Phase II Two Stage Finding Run-in Study of SAR3419, An Anti-CD19 Antibody-Maytansine Conjugate, Administered as a Single Agent by Intravenous Infusion in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia    Click to Show/Hide
Objective Response Rate (ORR)	NCT01470456	PHASE2	An Open Label, Multicenter Phase II Study of Intravenous SAR3419, an Anti-CD19 Antibody-Maytansine Conjugate, in Combination With Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphomas    Click to Show/Hide
Objective Response Rate (ORR)	NCT01472887	PHASE2	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma    Click to Show/Hide
Complete response (CR)	NCT01472887	PHASE2	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma    Click to Show/Hide
Undisclosed	NCT00549185	PHASE1	An Open-label Multi-dose-escalation, Safety and Pharmacokinetic Study of SAR3419 Administered as a Single Agent by Intravenous Infusion Every 3 Weeks in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (NHL)    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	stable disease (SD)	17.10%
Patients Enrolled	Eligible patients must have confirmed CD19+ DLBCL (de novo/transformed, >30% expression via recent biopsy) with ≥1 prior rituximab-containing regimen and relapsed/refractory status (post-1L ineligible for transplant or post-2L including ASCT). Exclusions cover primary refractory cases and mediastinal DLBCL. Archived FFPE tissue (≤6 months old) or fresh FNA is mandatory for eligibility assessment.    Click to Show/Hide
Administration Dosage	All patients will receive SAR3419 until evidence of disease progression, unacceptable toxicity, or other reasons for therapy discontinuation
Related Clinical Trial
NCT Number	NCT01472887	Clinical Status	PHASE2
Clinical Description	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma
Primary Endpoint	The primary outcome is the number of participants achieving Objective Response Rate, measured at 18 months.
Other Endpoint	Secondary measures include AE monitoring (up to 1 year), response duration, PFS, and OS (all assessed up to 18 months post-first infusion of the last patient). Key safety and efficacy parameters will be tracked longitudinally during this period.
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	stable disease (SD)	43%
Patients Enrolled	Eligible participants must have relapsed/refractory CD19+ B-cell NHL (excluding Burkitt's, lymphoblastic, or CLL) with prior standard treatment failure (including post-transplant cases). Exclusions include CNS involvement, non-measurable disease, ECOG >2, life expectancy <3 months, recent chemo/RT (4 weeks), prior radioimmunotherapy (12 weeks), protein anaphylaxis, HIV/HBV/HCV, organ dysfunction, pregnancy, inadequate contraception, or investigator-assessed safety risks.    Click to Show/Hide
Administration Dosage	The q1w study was extended to treat 25 pts with the optimized schedule for 8 to 12 doses.
Related Clinical Trial
NCT Number	NCT00796731	Clinical Status	PHASE1
Clinical Description	A Dose-escalation, Safety and Pharmacokinetic Study of SAR3419 Administered as a Single Agent by Intravenous Infusion Once Weekly in Patients With Relapsed/Refractory CD19-positive B-cell Non-Hodgkin's Lymphoma (NHL)
Primary Endpoint	The study will assess the incidence of Dose Limiting Toxicities (DLTs) at each tested dose level, with evaluation conducted within the first 3 weeks of treatment initiation.
Other Endpoint	Cumulative DLTs will be monitored throughout the entire treatment period, along with adverse events, lab abnormalities, tumor response (CR/PR), response duration, and pharmacokinetic parameters, all tracked for the duration of the study.
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	progressive disease (PD)	39%
Patients Enrolled	Eligible patients must have confirmed CD19+ DLBCL (de novo/transformed, >30% expression via recent biopsy) with &ge;1 prior rituximab-containing regimen and relapsed/refractory status (post-1L ineligible for transplant or post-2L including ASCT). Exclusions cover primary refractory cases and mediastinal DLBCL. Archived FFPE tissue (&le;6 months old) or fresh FNA is mandatory for eligibility assessment.    Click to Show/Hide
Administration Dosage	All patients will receive SAR3419 until evidence of disease progression, unacceptable toxicity, or other reasons for therapy discontinuation
Related Clinical Trial
NCT Number	NCT01472887	Clinical Status	PHASE2
Clinical Description	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma
Primary Endpoint	The primary outcome is the number of participants achieving Objective Response Rate, measured at 18 months.
Other Endpoint	Secondary measures include AE monitoring (up to 1 year), response duration, PFS, and OS (all assessed up to 18 months post-first infusion of the last patient). Key safety and efficacy parameters will be tracked longitudinally during this period.
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Partial Response (PR)	29.30%
Patients Enrolled	Eligible patients must have confirmed CD19+ DLBCL (de novo/transformed, >30% expression via recent biopsy) with &ge;1 prior rituximab-containing regimen and relapsed/refractory status (post-1L ineligible for transplant or post-2L including ASCT). Exclusions cover primary refractory cases and mediastinal DLBCL. Archived FFPE tissue (&le;6 months old) or fresh FNA is mandatory for eligibility assessment.    Click to Show/Hide
Administration Dosage	All patients will receive SAR3419 until evidence of disease progression, unacceptable toxicity, or other reasons for therapy discontinuation
Related Clinical Trial
NCT Number	NCT01472887	Clinical Status	PHASE2
Clinical Description	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma
Primary Endpoint	The primary outcome is the number of participants achieving Objective Response Rate, measured at 18 months.
Other Endpoint	Secondary measures include AE monitoring (up to 1 year), response duration, PFS, and OS (all assessed up to 18 months post-first infusion of the last patient). Key safety and efficacy parameters will be tracked longitudinally during this period.
Experiment 5 Reporting the Activity Date of This ADC					[7]
Efficacy Data	Objective Response Rate (ORR)	25.50%
Patients Enrolled	Eligible patients must have relapsed/refractory B-cell Acute Lymphoblastic Leukemia (including Burkitt's lymphoma), &le;3 prior salvage therapies, and CD19 positivity. Philadelphia-positive patients failing imatinib mesylate are included. No specific exclusion criteria were stated.
Administration Dosage	A total of 37 patients were enrolled from October 10, 2011 to December 19, 2013. One patient was included but did not receive the study treatment, leaving 36 treated patients in the safety population. Of the 36 patients, 19 were treated in part 1 of the study: 7 at 55 mg/m2; 4 at 70 mg/m2; and 8 at 90 mg/m2. The selected dose was determined as 70 mg/m2 and was used in part 2 of the study. As detailed, the 90-mg/m2 dose was associated with no improvement in ORR and an increased occurrence of AEs. An additional 17 patients were included and treated during part 2 of the study. All patients were expected to receive treatment at 70 mg/m2; however, 2 patients received the reduced dose of 55 mg/m2 owing to infusion-related toxicities.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT01440179	Clinical Status	PHASE2
Clinical Description	Phase II Two Stage Finding Run-in Study of SAR3419, An Anti-CD19 Antibody-Maytansine Conjugate, Administered as a Single Agent by Intravenous Infusion in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
Primary Endpoint	The study will assess the number of participants achieving an Objective Response Rate (ORR), with evaluations conducted every 4 to 8 weeks.
Other Endpoint	Safety will be monitored by tracking adverse events over one year, while pharmacokinetic parameters (Cmax, AUC, T1/2, clearance, Vss) will be analyzed for up to 8 months. Minimal Residual Disease (MRD) will also be evaluated every 4 to 8 weeks.
Experiment 6 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Objective Response Rate (ORR)	31.10%
Patients Enrolled	Eligibility requires a confirmed DLBCL diagnosis with CD19/CD20 positivity and prior rituximab-containing treatment failure. Exclusion criteria include absence of measurable disease (>1.5x1.5 cm lesion on CT) and other safety considerations per investigator assessment.
Administration Dosage	Patients received four weekly doses of coltuximab ravtansine (55 mg/m2) and rituximab (375 mg/m2) by intravenous infusion from weeks 1-4 followed by 4 biweekly doses on weeks 6, 8, 10 and 12.
Related Clinical Trial
NCT Number	NCT01470456	Clinical Status	PHASE2
Clinical Description	An Open Label, Multicenter Phase II Study of Intravenous SAR3419, an Anti-CD19 Antibody-Maytansine Conjugate, in Combination With Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphomas
Primary Endpoint	The primary endpoint is the number of participants achieving an Objective Response Rate, assessed at the 18-week mark.
Other Endpoint	Secondary objectives include monitoring adverse events (up to 6 months), response duration, progression-free survival, and overall survival (all tracked up to 24 months post-first infusion of the last enrolled patient).
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Objective Response Rate (ORR)	43.90%
Patients Enrolled	Eligible patients must have confirmed CD19+ DLBCL (de novo/transformed, >30% expression via recent biopsy) with &ge;1 prior rituximab-containing regimen and relapsed/refractory status (post-1L ineligible for transplant or post-2L including ASCT). Exclusions cover primary refractory cases and mediastinal DLBCL. Archived FFPE tissue (&le;6 months old) or fresh FNA is mandatory for eligibility assessment.    Click to Show/Hide
Administration Dosage	All patients will receive SAR3419 until evidence of disease progression, unacceptable toxicity, or other reasons for therapy discontinuation
Related Clinical Trial
NCT Number	NCT01472887	Clinical Status	PHASE2
Clinical Description	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma
Primary Endpoint	The primary outcome is the number of participants achieving Objective Response Rate, measured at 18 months.
Other Endpoint	Secondary measures include AE monitoring (up to 1 year), response duration, PFS, and OS (all assessed up to 18 months post-first infusion of the last patient). Key safety and efficacy parameters will be tracked longitudinally during this period.
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Complete response (CR)	14.60%
Patients Enrolled	Eligible patients must have confirmed CD19+ DLBCL (de novo/transformed, >30% expression via recent biopsy) with &ge;1 prior rituximab-containing regimen and relapsed/refractory status (post-1L ineligible for transplant or post-2L including ASCT). Exclusions cover primary refractory cases and mediastinal DLBCL. Archived FFPE tissue (&le;6 months old) or fresh FNA is mandatory for eligibility assessment.    Click to Show/Hide
Administration Dosage	All patients will receive SAR3419 until evidence of disease progression, unacceptable toxicity, or other reasons for therapy discontinuation
Related Clinical Trial
NCT Number	NCT01472887	Clinical Status	PHASE2
Clinical Description	An Open Label Non-Randomized Phase 2 Study Evaluating SAR3419, an Anti-CD19 Antibody - Maytansine Conjugate, Administered as Single Agent by Intravenous Infusion to Patients With Relapsed or Refractory CD19+ Diffuse Large B-Cell Lymphoma
Primary Endpoint	The primary outcome is the number of participants achieving Objective Response Rate, measured at 18 months.
Other Endpoint	Secondary measures include AE monitoring (up to 1 year), response duration, PFS, and OS (all assessed up to 18 months post-first infusion of the last patient). Key safety and efficacy parameters will be tracked longitudinally during this period.
Experiment 9 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Eligible participants must have relapsed/refractory CD19+ non-Hodgkin's B-cell lymphoma (excluding Burkitt's, lymphoblastic, or CLL) with ECOG 0-2. Exclusions include recent chemotherapy/radiotherapy (4 weeks), prior radioimmunotherapy (12 weeks), protein/maytansinoid intolerance, organ dysfunction, pregnancy, or inadequate contraception. Investigator-assessed high-risk comorbidities also preclude participation.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT00549185	Clinical Status	PHASE1
Clinical Description	An Open-label Multi-dose-escalation, Safety and Pharmacokinetic Study of SAR3419 Administered as a Single Agent by Intravenous Infusion Every 3 Weeks in Patients With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (NHL)
Primary Endpoint	The study evaluates Dose Limiting Toxicities (DLTs) across tested dose levels throughout the entire study period.
Other Endpoint	Tumor response (complete/partial/stable disease) will be assessed per Cheson criteria alongside response duration, while adverse events will be monitored continuously during the study.

Ref 1	A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma
Ref 2	A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
Ref 3	Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma
Ref 4	Design of Coltuximab Ravtansine, a CD19-Targeting Antibody-Drug Conjugate (ADC) for the Treatment of B-Cell Malignancies: Structure-Activity Relationships and Preclinical Evaluation
Ref 5	SAR3419 as Single Agent in Relapsed-Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Patients
Ref 6	SAR3419 Administered Weekly in Patients With Relapsed/Refractory CD19-positive B-cell Non-Hodgkin's Lymphoma
Ref 7	SAR3419 in Acute Lymphoblastic Leukemia
Ref 8	Multi-dose-escalation Safety and Pharmacokinetic Study of SAR3419 as Single Agent in Relapsed/Refractory B-cell Non Hodgkin's Lymphoma