Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0HISTV
ADC Name
AVE9633
Synonyms
AVE9633; HuMy9-6-DM4; DCLL-9718S
   Click to Show/Hide
Organization
ImmunoGen (Top20 MNC) (Originator) (No Rights);Sanofi (Top20 MNC)
Drug Status
Phase 1 (discontinued)
Drug-to-Antibody Ratio
3.5
Structure
Antibody Name
HuMy9-6
  Antibody Info 
Antigen Name
Myeloid cell surface antigen CD33 (CD33)
  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
The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
Indication Phase 1 Phase 1/2 Phase 2 Phase 2/3 Phase 3 New Drug Application Approved
Acute myeloid leukaemia
1 Trials
Trial ID
NCT00543972; EudraCT2006-005976-41
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 14 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 7.36 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 11.4 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 14.8 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 33.6 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 21.8 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 58.3 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 32.5 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 66 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 40.9 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 170 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 113 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 382 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Maximum Observed Concentration (Cmax) 119 ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 468 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Distribution
Click To Hide/Show 14 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 11.4 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Volume of Distribution (Vd) 3.62 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 33.6 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Volume of Distribution (Vd) 3.92 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 58.3 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Volume of Distribution (Vd) 3.97 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 66 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Volume of Distribution (Vd) 4.46 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 170 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Volume of Distribution (Vd) 3.29 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 382 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Volume of Distribution (Vd) 4.81 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 468 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Volume of Distribution (Vd) 4.77 L
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Metabolism
Click To Hide/Show 7 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 11.4 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 33.6 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 58.3 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 66 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 170 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 382 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 468 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Excretion
Click To Hide/Show 21 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 11.4 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Elimination Half-Life (t1/2) 1.06 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Clearance (CL) 2.75 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 15 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 33.6 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Elimination Half-Life (t1/2) 1.59 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Clearance (CL) 2 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 30 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 58.3 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Elimination Half-Life (t1/2) 1.93 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Clearance (CL) 1.66 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 50 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 66 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Elimination Half-Life (t1/2) 1.59 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Clearance (CL) 2.11 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 75 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 170 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Elimination Half-Life (t1/2) 2.17 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Clearance (CL) 1.06 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 105 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 382 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Elimination Half-Life (t1/2) 3.81 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Clearance (CL) 1.12 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 200 mg/m2.
 [1]
Area Under the Concentration-Time Curve (AUC) 468 day*ug/mL
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Elimination Half-Life (t1/2) 3.93 day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
Clearance (CL) 0.883 L/day
PK parameters of huMy9-6-DM4 during Cycle 1 in evaluable patients, 260 mg/m2.
 [1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT00543972
PHASE1
An Open Label, Dose-Escalation Safety and Pharmacokinetic Study of AVE9633 Administered as a Single Agent by Intravenous Infusion on Day 1, Day 4 and Day 7 of a 4-Week Cycle in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia (AML)

   Click to Show/Hide
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Inclusion: CD33+ relapsed/refractory AML patients (no curative options) with ECOG 0-2. Exclusion: Recent gemtuzumab ozogamicin/allogenic transplant (≤6 months), anticancer therapy ≤3 weeks (hydroxyurea/leukophoresis allowed), prior AVE9633 exposure, organ dysfunction, comorbidities affecting safety, pregnancy/lactation, or inadequate contraception.

   Click to Show/Hide
Administration Dosage
AVE9633 was administered at increasing doses using three treatment schedules, as outlined in Table 1. In the initial trial (so-called "Day 1 study") 22 patients received 15 to 260 mg/m2 on day 1 of a 21-day cycle. Following the completion of the first dose levels, two other trials were initiated; 20 patients received 30 to 150 mg/m2 on day 1 and day 8 of a 28-day cycle (Day 1/8 study) and 12 patients received 30 to 90 mg/m2 on day 1, day 4 and day 7 of a 28-day cycle (Day 1/4/7 study).

   Click to Show/Hide
Related Clinical Trial
NCT Number NCT00543972  Clinical Status PHASE1
Clinical Description An Open Label, Dose-Escalation Safety and Pharmacokinetic Study of AVE9633 Administered as a Single Agent by Intravenous Infusion on Day 1, Day 4 and Day 7 of a 4-Week Cycle in Patients With Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia (AML)
Primary Endpoint
The primary outcome is incidence of Dose Limiting Toxicities (DLTs) across tested dose levels during the study period.
Other Endpoint
Efficacy endpoints include Complete Remission (CR), CR with incomplete platelet recovery (CRp), Partial Remission (PR) rates, time to/duration of CR, and peripheral blast clearance. Safety is assessed through Adverse Events (AEs).
References
Ref 1 Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia
Ref 2 Dose Escalation Safety and Pharmacokinetic Study of AVE9633 as Single Agent in Relapsed/Refractory CD33-Positive Acute Myeloid Leukemia