Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0XJCNE
ADC Name
AMT-253
Synonyms
AMT-253
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Organization
Multitude Therapeutics (Originator)
Drug Status
Phase 1/2
Drug-to-Antibody Ratio
8
Structure
Antibody Name
Anti-MUC18 IgG1 mAb
  Antibody Info 
Antigen Name
Cell surface glycoprotein MUC18 (MCAM)
  Antigen Info 
Payload Name
Exatecan
  Payload Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
  Target Info 
Linker Name
T1000
  Linker Info 
Conjugate Type
Random Cysteines
Combination Type
sesutecan
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
Unspecific solid tumor
1 Trials
Trial ID
NCT06209580; NCT05906862; CTR20234311
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 27 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Time to Maximum Concentration (Tmax) 0.25 h
PK parapaters in A375 tumor-bearing mice
 [1]
Maximum Observed Concentration (Cmax) 110 ug/mL
PK parapaters in A375 tumor-bearing mice
 [1]
Area Under the Concentration-Time Curve (AUC) 6941 ug*h/mL
PK parapaters in A375 tumor-bearing mice, AUC0-t.
 [1]
Time to Maximum Concentration (Tmax) 0.0833 h
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1.
 [1]
Maximum Observed Concentration (Cmax) 292.4 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 16300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 16368 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 0.0833 h
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22.
 [1]
Maximum Observed Concentration (Cmax) 352 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 9207 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 9211 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 2.05 h
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1.
 [1]
Maximum Observed Concentration (Cmax) 944.5 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 81100 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 84700 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 1.1 h
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22.
 [1]
Maximum Observed Concentration (Cmax) 871.5 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 91300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 100150 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 1.1 h
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1.
 [1]
Maximum Observed Concentration (Cmax) 1480 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 138500 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 143000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCinf.
 [1]
Time to Maximum Concentration (Tmax) 4.05 h
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22.
 [1]
Maximum Observed Concentration (Cmax) 1141.5 ug/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 135000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 138000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCinf.
 [1]
Distribution
Click To Hide/Show 13 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 6941 ug*h/mL
PK parapaters in A375 tumor-bearing mice, AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 16300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 16368 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 9207 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 9211 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 81100 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 84700 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 91300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 100150 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 138500 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 143000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 135000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 138000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCinf.
 [1]
Metabolism
Click To Hide/Show 13 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 6941 ug*h/mL
PK parapaters in A375 tumor-bearing mice, AUC0-t.
 [1]
Area Under the Concentration-Time Curve (AUC) 16300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 16368 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 9207 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 9211 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 81100 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 84700 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 91300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 100150 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 138500 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 143000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCinf.
 [1]
Area Under the Concentration-Time Curve (AUC) 135000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 138000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCinf.
 [1]
Excretion
Click To Hide/Show 20 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Elimination Half-Life (t1/2) 119 h
PK parapaters in A375 tumor-bearing mice
 [1]
Area Under the Concentration-Time Curve (AUC) 6941 ug*h/mL
PK parapaters in A375 tumor-bearing mice, AUC0-t.
 [1]
Elimination Half-Life (t1/2) 43 h
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 16300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 16368 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 1, AUCinf.
 [1]
Elimination Half-Life (t1/2) 23.7 h
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 9207 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 9211 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 10 mg/kg, Day 22, AUCinf.
 [1]
Elimination Half-Life (t1/2) 104.8 h
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 81100 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 84700 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 1, AUCinf.
 [1]
Elimination Half-Life (t1/2) 122.95 h
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 91300 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 100150 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 45 mg/kg, Day 22, AUCinf.
 [1]
Elimination Half-Life (t1/2) 101.35 h
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 138500 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 143000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 1, AUCinf.
 [1]
Elimination Half-Life (t1/2) 98.55 h
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 135000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCtau.
 [1]
Area Under the Concentration-Time Curve (AUC) 138000 ug*h/mL
PK parameters of Non-GLP toxicity study in Monkeys, 60 mg/kg, Day 22, AUCinf.
 [1]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT05117138
PHASE1|||PHASE2
Safety and Efficacy of Chimeric Antigen Receptor T Lymphocytes for Patients With Intermediate and Advanced Tumors
Undisclosed  NCT06209580
PHASE1|||PHASE2
Phase I/II Study of AMT-253 in Patients With Unresectable or Metastatic Malignant Melanoma and Other Advanced Solid Tumors
Undisclosed  NCT05906862
PHASE1
First-in-Human, Phase 1 Study of AMT-253, in Patients With Advanced Solid Tumors
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Eligible patients aged 18-70 with histopathologically confirmed melanoma, non-small cell lung cancer (squamous), or head/neck squamous cell carcinoma must meet specific criteria including target protein expression, adequate venous access, and proper blood/liver/kidney function; exclusion factors cover active infections, prior CAR-T therapy, immunosuppressant use, severe systemic/autoimmune diseases, pregnancy, allergies, or prior organ transplants.

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Administration Dosage
.
Related Clinical Trial
NCT Number NCT05117138  Clinical Status PHASE1|||PHASE2
Clinical Description Safety and Efficacy of Chimeric Antigen Receptor T Lymphocytes for Patients With Intermediate and Advanced Tumors
Primary Endpoint
Primary endpoints include incidence of adverse events, overall response rate (ORR), and one-year recurrence rate, all evaluated over a 24-week timeframe.
Other Endpoint
Secondary endpoints comprise progression-free survival (PFS) and relapse-free survival (RFS), also measured within a 24-week period.
Experiment 2 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Eligibility requires signed ICF, advanced solid tumors, progression after prior therapy, measurable lesions, ECOG 0-1, ≥3 month life expectancy, adequate organ function, and contraceptive use. Exclusions include prior target therapy, CNS metastases, severe skin disorders, unresolved toxicities (>Grade 1), recent treatments/surgeries, cardiac issues, thromboembolic events, active infections, or recent live vaccines.

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Administration Dosage
Administered intravenously
Related Clinical Trial
NCT Number NCT06209580  Clinical Status PHASE1|||PHASE2
Clinical Description Phase I/II Study of AMT-253 in Patients With Unresectable or Metastatic Malignant Melanoma and Other Advanced Solid Tumors
Primary Endpoint
The study assesses DLTs (21 days post-dose), AEs/SAEs (24 months) including type, incidence and severity, and ORR per RECIST 1.1.
Other Endpoint
Pharmacokinetic metrics over 24 months include Cmax, Tmax, AUC, t1/2 of ADC components, and ADA quantification.
Experiment 3 Reporting the Activity Date of This ADC [4]
Patients Enrolled
Eligible patients must be ≥18 years, with progressive disease after systemic therapy, measurable lesions per RECIST v1.1, ECOG 0-1, adequate organ function, and life expectancy ≥3 months. Key exclusions include CNS metastasis, active infections, significant cardiac/autoimmune diseases, recent major surgery/radiotherapy, unresolved toxicities >Grade 1, pregnancy, or prior malignancies within 5 years (unless inclusion-related). Contraception and tumor tissue availability are required.

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Administration Dosage
Administered intravenously
Related Clinical Trial
NCT Number NCT05906862  Clinical Status PHASE1
Clinical Description First-in-Human, Phase 1 Study of AMT-253, in Patients With Advanced Solid Tumors
Primary Endpoint
The study focuses on determining the Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) based on dose-limiting toxicities (DLTs) and other data over 24 months. Safety and tolerability will be assessed using Common Terminology Criteria for Adverse Events v5.0 to evaluate adverse event types, incidence, and severity.
Other Endpoint
Key efficacy endpoints include Overall Response Rate (ORR) and Disease Control Rate (DCR) per RECIST v1.1, along with Progression-free Survival (PFS). Pharmacokinetic profiling will assess Cmax, AUC, terminal half-life (t1/2), and Tmax of AMT-253, while immunogenicity will be evaluated via anti-drug antibody (ADA) concentrations, all measured over 24 months.

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References
Ref 1 A Cell Surface-Binding Antibody Atlas Nominates a MUC18-Directed Antibody-Drug Conjugate for Targeting Melanoma
Ref 2 Safety and Efficacy of Chimeric Antigen Receptor T Lymphocytes for Patients With Intermediate and Advanced Tumors
Ref 3 AMT-253 in Patients With Advanced Solid Tumours
Ref 4 AMT-253 in Patients With Selected Advanced Solid Tumours