Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0SQXAL
ADC Name
ARX-517
Synonyms
ARX 517; ARX-517; ARX517
   Click to Show/Hide
Organization
Ambrx, Inc.
Drug Status
Phase 1
Drug-to-Antibody Ratio
2
Structure
Antibody Name
Humanized anti-PSMA IgG1k mAb
  Antibody Info 
Antigen Name
Glutamate carboxypeptidase 2 (FOLH1)
  Antigen Info 
Payload Name
Amberstatin-269
  Payload Info 
Linker Name
Oxime-PEG3
  Linker Info 
Conjugate Type
Site-specific conjugation through unnatural amino acid (pAF 121).
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
Prostate cancer
1 Trials
Trial ID
NCT04662580
General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
Click To Hide/Show 32 Absorption Data Related to This Level
Standard Type Value Units Description Reference
Maximum Observed Concentration (Cmax) 10500 ng/mL
ARX517 PK parameters in mice without tumor, 1 mg/kg.
 [2]
Maximum Observed Concentration (Cmax) 57000 ng/mL
ARX517 PK parameters in mice without tumor, 5 mg/kg.
 [2]
Maximum Observed Concentration (Cmax) 10800 ng/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg.
 [2]
Maximum Observed Concentration (Cmax) 57100 ng/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg.
 [2]
Area Under the Concentration-Time Curve (AUC) 1550000 ng*h/mL
ARX517 PK parameters in mice without tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7380000 ng*h/mL
ARX517 PK parameters in mice without tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 1330000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7570000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg, AUClast.
 [2]
Maximum Observed Concentration (Cmax) 24900 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male.
 [2]
Maximum Observed Concentration (Cmax) 23800 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female.
 [2]
Maximum Observed Concentration (Cmax) 175000 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male.
 [2]
Maximum Observed Concentration (Cmax) 152000 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female.
 [2]
Maximum Observed Concentration (Cmax) 266000 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male.
 [2]
Maximum Observed Concentration (Cmax) 243000 ng/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male.
 [2]
Time to Maximum Concentration (Tmax) 0.5 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female.
 [2]
Area Under the Concentration-Time Curve (AUC) 2870000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 3300000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 36500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 35100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 44100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 47000000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 2130000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 2350000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 19800000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 16500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 29600000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 26500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUC0-168h.
 [2]
Distribution
Click To Hide/Show 16 Distribution Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1550000 ng*h/mL
ARX517 PK parameters in mice without tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7380000 ng*h/mL
ARX517 PK parameters in mice without tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 1330000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7570000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 2870000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 3300000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 36500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 35100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 44100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 47000000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 2130000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 2350000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 19800000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 16500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 29600000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 26500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUC0-168h.
 [2]
Metabolism
Click To Hide/Show 16 Metabolism Data Related to This Level
Standard Type Value Units Description Reference
Area Under the Concentration-Time Curve (AUC) 1550000 ng*h/mL
ARX517 PK parameters in mice without tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7380000 ng*h/mL
ARX517 PK parameters in mice without tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 1330000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7570000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 2870000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 3300000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 36500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 35100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 44100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 47000000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 2130000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 2350000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 19800000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 16500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 29600000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 26500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUC0-168h.
 [2]
Excretion
Click To Hide/Show 27 Excretion Data Related to This Level
Standard Type Value Units Description Reference
Elimination Half-Life (t1/2) 6-10 day
ARX517 exhibited virtually overlapping TA and ADC PK concentration-time curves at all dose levels tested, indicating strong stability of the ADC with minimal premature payload release. A long ADC terminal half-life of 6-10 days was observed at doses ≥ 1.4 mg/kg, thereby maximizing drug exposure over a dosing cycle of 3 weeks.

   Click to Show/Hide
 [1]
Area Under the Concentration-Time Curve (AUC) 1550000 ng*h/mL
ARX517 PK parameters in mice without tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7380000 ng*h/mL
ARX517 PK parameters in mice without tumor, 5 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 1330000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 7570000 ng*h/mL
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg, AUClast.
 [2]
Elimination Half-Life (t1/2) 261 h
ARX517 PK parameters in mice without tumor, 1 mg/kg.
 [2]
Elimination Half-Life (t1/2) 350 h
ARX517 PK parameters in mice without tumor, 5 mg/kg.
 [2]
Elimination Half-Life (t1/2) 210 h
ARX517 PK parameters in mice bearing C4-2 tumor, 1 mg/kg.
 [2]
Elimination Half-Life (t1/2) 237 h
ARX517 PK parameters in mice bearing C4-2 tumor, 5 mg/kg.
 [2]
Area Under the Concentration-Time Curve (AUC) 2870000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 3300000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 36500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 35100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 44100000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUClast.
 [2]
Area Under the Concentration-Time Curve (AUC) 47000000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUClast.
 [2]
Elimination Half-Life (t1/2) 151 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male.
 [2]
Elimination Half-Life (t1/2) 135 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female.
 [2]
Elimination Half-Life (t1/2) 324 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male.
 [2]
Elimination Half-Life (t1/2) 315 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female.
 [2]
Elimination Half-Life (t1/2) 284 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male.
 [2]
Elimination Half-Life (t1/2) 308 h
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female.
 [2]
Area Under the Concentration-Time Curve (AUC) 2130000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 2350000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 1 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 19800000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 16500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 6 mg/kg, Female, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 29600000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Male, AUC0-168h.
 [2]
Area Under the Concentration-Time Curve (AUC) 26500000 ng*h/mL
ARX517 TK parameters in cynomolgus monkey repeat-dose toxicity study, 9 mg/kg, Female, AUC0-168h.
 [2]
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT04662580
PHASE1
A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer

   Click to Show/Hide
Undisclosed  NCT04662580
Phase 1/2
A phase 1/2, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, pharmacokinetics, and anti-tumor activity of ARX517, with randomized comparison to investigator's choice of treatment, in subjects with metastatic castration-resistant prostate cancer who are resistant or refractory to prior standard therapies.

   Click to Show/Hide
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Patients Enrolled
Major exclusions include recent chemotherapy/hormonal/radiation therapy (varies by cohort), prior taxanes or ARPIs (specific to cohorts), corticosteroid use (>10mg prednisone equivalent), active CNS metastases, other malignancies (last 2 years), QTc >480ms, lung disease (last 12 months), ocular disorders, grade ≥2 neuropathy, and proteinuria (>1g/24h). Seizure history disqualifies for apalutamide combination cohorts.

   Click to Show/Hide
Administration Dosage
ARX517 will be administered via intravenous (IV) infusion, with the initial treatment regimen by weight-based infusion at an interval of every 3 weeks. Other treatment regimen may be explored.
Related Clinical Trial
NCT Number NCT04662580  Clinical Status PHASE1
Clinical Description A Phase 1, Multicenter, Open-Label, Dose-Escalation, and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of ARX517 as Monotherapy and in Combination With Androgen Receptor Pathway Inhibitors in Subjects With Metastatic Prostate Cancer
Primary Endpoint
The study will assess safety and tolerability of ARX517 (alone or combined with ARPIs) through adverse event incidence/severity (CTCAE v5) over 1.5 years, alongside pharmacokinetic parameters (AUC, Cmax, Ctrough) and immunogenicity (ADA incidence) over 3 years. Efficacy endpoints include overall survival (OS), PSA response rates (PSA30/50/90), and progression-free survival (PFS).

   Click to Show/Hide
Other Endpoint
Key inclusion criteria require males ≥18 with prostate adenocarcinoma, adequate LHRH therapy (testosterone ≤50ng/dL for mCRPC), prior treatments per cohort, documented progression (mCRPC) or high-volume metastases (mCSPC), and PSMA-positive lesions. Adequate hematologic/organ function and PSMA PET eligibility are mandatory.
Experiment 2 Reporting the Activity Date of This ADC [4]
Related Clinical Trial
NCT Number NCT04662580  Clinical Status Phase 1/2
Clinical Description A phase 1/2, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, pharmacokinetics, and anti-tumor activity of ARX517, with randomized comparison to investigator's choice of treatment, in subjects with metastatic castration-resistant prostate cancer who are resistant or refractory to prior standard therapies.
References
Ref 1 ADCT-701, a novel pyrrolobenzodiazepine (PBD) dimer-based antibody-drug conjugate (ADC)targeting DLK1-expressing tumors
Ref 2 Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody-Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Ref 3 ARX517/JNJ-95298177 as Monotherapy or Combination Therapy in Subjects With Metastatic Prostate Cancer
Ref 4 A Phase 1/2, Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of ARX517, With Randomized Comparison to Investigator's Choice of Treatment, in Subjects With Metastatic Castration-resistant Prostate Cancer Who Are Resistant or Refractory to Prior Standard Therapies, NCT04662580