Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0YDZSG
ADC Name
AMT-562
Synonyms
AMT-562
   Click to Show/Hide
Organization
Multitude Therapeutics (Originator)
Drug Status
Phase 1
Drug-to-Antibody Ratio
8
Structure
Antibody Name
Ab562
  Antibody Info 
Antigen Name
Receptor tyrosine-protein kinase erbB-3 (ERBB3); Tumor-associated calcium signal transducer 2 (TACSTD2)
  Antigen Info 
Payload Name
Exatecan
  Payload Info 
Therapeutic Target
DNA topoisomerase 1 (TOP1)
  Target Info 
Linker Name
T800
  Linker Info 
Conjugate Type
Random Cysteines
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
NCT06199908
ADC-specific functional property(2027 Update)
Bystander Killing Effect
Click To Hide/Show 1 ADC-specific functional property Data
Bystander Killing Effect Description Reference
yes
AMT-562's bystander killing efficacy was measured using an in vitro culture system with single or cocultures of HER3- (COLO320DM) and HER3+ (PC9GR) cell lines (Fig. 3A; Supplementary Fig. S8E and S8F). After 5 days of incubation, cells were sorted for HER3 expression by flow cytometry (Supplementary Fig. S8E). AMT-562 killed HER3-COLO320DM cells efficiently (Fig. 3A; Supplementary Fig. S8E). Negative control ADCs did not induce cell killing compared with untreated wells, confirming the bystander killing effect of AMT-562. In comparison, P-GGFG-DXd showed less cytotoxicity and bystander killing was not significant versus isotype ADC control (Fig. 3A).

   Click to Show/Hide
[1]
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 8 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 754 ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 1.
 [1]
Maximum Observed Concentration (Cmax) 614 ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 22.
 [1]
Maximum Observed Concentration (Cmax) 556 ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 43.
 [1]
Area Under the Concentration-Time Curve (AUC) 1670 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 1369 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 1127 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 43.
 [1]
Area Under the Concentration-Time Curve (AUC) 426.17±54.7 day*ug/mL
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Maximum Observed Concentration (Cmax) 124.99±10 ug/mL
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Distribution
Click To Hide/Show 5 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1670 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 1369 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 1127 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 43.
 [1]
Area Under the Concentration-Time Curve (AUC) 426.17±54.7 day*ug/mL
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Volume of Distribution (Vd) 125.06±8.4 mL/kg
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Metabolism
Click To Hide/Show 4 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1670 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 1369 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 1127 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 43.
 [1]
Area Under the Concentration-Time Curve (AUC) 426.17±54.7 day*ug/mL
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Excretion
Click To Hide/Show 9 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1670 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 1.
 [1]
Area Under the Concentration-Time Curve (AUC) 1369 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 22.
 [1]
Area Under the Concentration-Time Curve (AUC) 1127 day*ug/mL
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), AUC0-t, Day 43.
 [1]
Elimination Half-Life (t1/2) 2.1 day
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 1.
 [1]
Elimination Half-Life (t1/2) 2.2 day
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 22.
 [1]
Elimination Half-Life (t1/2) 2 day
Pharmacokinetic data of AMT-562 from repeated dose toxicity studies in cynomolgus monkeys. ADCs were intravenously administered to cynomolgus monkeys at the dose of 30 mg/kg (n = 2), Day 43.
 [1]
Area Under the Concentration-Time Curve (AUC) 426.17±54.7 day*ug/mL
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Elimination Half-Life (t1/2) 3.92±1.3 day
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [1]
Clearance (CL) 23.14±3.5 mL/day/kg
Single dose pharmacokinetic profiles of AMT-562 in mice. ADCs were intravenously administered to mice at the dose of 10 mg/kg (n = 3).
 [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  NCT06199908
PHASE1
First-in-Human, Phase 1 Study of AMT-562 in Patients With Advanced Solid Tumors
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Standard Type Value Units Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI) 
≈ 71.8
%
Pancreatic cancer PDX model (PDX: PDX-200930)
Tumor Growth Inhibition value (TGI) 
≈ 100
%
Pancreatic cancer PDX model (PDX: PDX-361319)
Tumor Growth Inhibition value (TGI) 
≈ 100
%
Squamous cell carcinoma PDX model (PDX: PDX-361318)
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
Eligible patients must be ≥18 years with histologically confirmed unresectable advanced solid tumors, prior systemic therapy failure, ECOG 0-1, adequate organ function, and at least one measurable lesion. Key exclusions include CNS metastasis, unresolved toxicities from prior therapy, active infections, recent major surgery or radiotherapy, significant cardiac disease, or concurrent investigational trial participation. Pregnancy, substance abuse, and uncontrolled medical/psychiatric conditions also disqualify candidates.

   Click to Show/Hide
Administration Dosage
Administered AMT-562 for injection intravenously
Related Clinical Trial
NCT Number NCT06199908  Clinical Status PHASE1
Clinical Description First-in-Human, Phase 1 Study of AMT-562 in Patients With Advanced Solid Tumors
Primary Endpoint
The study assesses safety endpoints including Dose Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs), evaluated for type, incidence, and severity over a 24-month timeframe.
Other Endpoint
Pharmacokinetic parameters such as Cmax, Tmax, AUC, t1/2, and Anti-Drug Antibodies (ADAs) are measured, alongside efficacy outcomes including ORR, DCR, PFS, TTR, and DOR, all assessed per RECIST v1.1 over 24 months.
Discovered Using Patient-derived Xenograft Model
Click To Hide/Show 3 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 71.80% Low HER3 expression (HER3+)
Method Description
AMT-562 (10 mg/kg, day 1) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-200930)
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Low HER3 expression (HER3+)
Method Description
AMT-562 (10 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Pancreatic cancer PDX model (PDX: PDX-361319)
Experiment 3 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100% Low HER3 expression (HER3+)
Method Description
AMT-562 (10 m ug/kg, every seven days x3) induces efficient tumor cell killing in cell line-derived models of Pancreatic cancer cell with HER3 expression with high expression.
In Vivo Model Squamous cell carcinoma PDX model (PDX: PDX-361318)
References
Ref 1 AMT-562, a Novel HER3-targeting Antibody-Drug Conjugate, Demonstrates a Potential to Broaden Therapeutic Opportunities for HER3-expressing Tumors
Ref 2 AMT-562 in Patients With Selected Advanced Solid Tumors
Ref 3 AMT-562, a novel HER3-targeting antibody drug conjugate, demonstrates a potential to broaden therapeutic opportunities for HER3-expressing tumors. Mol Cancer Ther. 2023 Jun 11:MCT-23-0198. doi: 10.1158/1535-7163.MCT-23-0198. Online ahead of print.