Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0RMBUN
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| ADC Name |
IMGC-936
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| Synonyms |
AEX6003 (S442C)-DGN549; IMGC 936; IMGC-936; IMGC936
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| Organization |
ImmunoGen, Inc.; MacroGenics, Inc.
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| Drug Status |
Phase 1/2
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| Drug-to-Antibody Ratio |
2
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| Structure |
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| Antibody Name |
MGA021
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Antibody Info | ||||
| Antigen Name |
Disintegrin and metalloproteinase domain-containing protein 9 (ADAM9)
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Antigen Info | ||||
| Payload Name |
DM21-C
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Ala-Ala-Ala
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Linker Info | ||||
| Conjugate Type |
Site-specific conjugation through the engineered cysteine 442 (CYSMAB).
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| Combination Type |
Tapatansine
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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 | ||
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| Unspecific solid tumor |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Maximum Observed Concentration (Cmax) | 41.9 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3380 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Maximum Observed Concentration (Cmax) | 41.4 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2120 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
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[1] |
| Maximum Observed Concentration (Cmax) | 222 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 23400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
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[1] |
| Maximum Observed Concentration (Cmax) | 380 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
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[1] |
| Maximum Observed Concentration (Cmax) | 714 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 67400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Maximum Observed Concentration (Cmax) | 738 | ug/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 56000 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
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[1] |
| Maximum Observed Concentration (Cmax) | 34.78 | ug/mL |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1966.35 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 3380 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2120 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 23400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 67400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 56000 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 1966.35 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 3380 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2120 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 23400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 67400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 56000 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 1966.35 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 3380 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Elimination Half-Life (t1/2) | 56.5 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Clearance (CL) | 1.16 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2120 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
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[1] |
| Elimination Half-Life (t1/2) | 41.1 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
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[1] |
| Clearance (CL) | 3.03 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 3 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 23400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
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[1] |
| Elimination Half-Life (t1/2) | 171 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
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[1] |
| Clearance (CL) | 0.32 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 1.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
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[1] |
| Elimination Half-Life (t1/2) | 98.7 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
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[1] |
| Clearance (CL) | 0.36 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 10 mg/kg, Day 15.
|
[1] |
| Area Under the Concentration-Time Curve (AUC) | 67400 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Elimination Half-Life (t1/2) | 283 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Clearance (CL) | 0.2 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 1.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 56000 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
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[1] |
| Elimination Half-Life (t1/2) | 95.2 | h |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
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[1] |
| Clearance (CL) | 0.35 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following repeat intravenous administration of IMGC936 to cynomolgus monkeys determined by non-compartmental analysis (NCA). 22.5 mg/kg, Day 15.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1966.35 | ug*h/mL |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
| Elimination Half-Life (t1/2) | 109.16 | h |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
| Clearance (CL) | 2.44 | mL/h/kg |
Conjugated antibody pharmacokinetic parameters following intravenous administration of IMGC936 in immunodeficient (CD-1 nude) mice by non-compartmental analysis (NCA).
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[1] |
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT04622774 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1/2, first-in-human, open-label, dose-escalation and expansion study of IMGC936 (Anti-ADAM9 antibody drug conjugate) in patients with advanced solid tumors. | ||||
| Primary Endpoint |
During dose escalation measure incidence and severity of Treatment Emergent Adverse Events, During dose escalation characterize dose-limiting toxicities (DLTs), During expansion describe the overall response rate.
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| Other Endpoint |
During dose escalation and expansion to characterize study drug concentration and the concentration of anti-drug antibody, During dose expansion describe the duration of response and progression free survival, During dose escalation to describe the objective response rate and duration of response, During dose expansion measure incidence and severity of Treatment Emergent Adverse Events.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Inclusion: Adults (≥18) with relapsed/refractory metastatic NSCLC (1-4 prior lines), TNBC (1-4 lines), CRC/GE/pancreatic cancer (1-3 lines), ECOG 0-1, adequate organ function (ANC≥1.5K/uL, platelets≥75K/uL, ALT/AST≤3×ULN, eGFR>30mL/min). Exclusion: Active CNS/ocular/cardiovascular disease (LVEF<50%, QTc>480ms), recent anticancer therapy (4w systemic/6w radiation), uncontrolled infections (HBV/HCV/COVID-19), or live vaccinations within 4w. Contraception required for 28w post-treatment.
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| Administration Dosage |
Participants received IMGC936 0.5, 1.0, 2.0, 4.0, 5.0, 6.0, 7.0 milligrams (mg)/kilogram (kg) via IV infusion on Day 1 of Cycle 1 and every subsequent 21-day cycle thereafter.
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| Related Clinical Trial | |||||
| NCT Number | NCT04622774 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation and Expansion Study of IMGC936 (Anti-ADAM9 Antibody Drug Conjugate) in Patients With Advanced Solid Tumors | ||||
| Primary Endpoint |
Primary endpoints include TEAEs/SAEs monitoring (up to 3 years) and DLT assessment per CTCAE v5.0 (Cycle 1: 21/28 days) with hematologic/non-hematologic criteria including Grade 4 neutropenia/thrombocytopenia, ≥Grade 3 ocular/hepatic events, and Hy's law cases. Dose expansion phase evaluates ORR per RECIST v1.1 (CR: complete lesion disappearance; PR: ≥30% target lesion reduction).
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| Other Endpoint |
Secondary objectives comprise PK analysis (Cmax), ADA incidence, ORR/DOR/PFS per RECIST v1.1 (PD: ≥20% target lesion increase +5mm absolute growth), and safety monitoring (TEAEs leading to discontinuation). DOR/PFS analyzed via Kaplan-Meier method.
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References