Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0WLYOR
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| ADC Name |
MLN2704
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| Synonyms |
MLN2704; DM1 conjugated monoclonal antibody MLN591
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| Organization |
Millennium Pharmaceuticals (Top20 MNC) (Originator)
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| Drug Status |
Phase 1/2 (discontinued)
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| Drug-to-Antibody Ratio |
3~4
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| Structure |
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| Antibody Name |
MLN591
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Antibody Info | ||||
| Antigen Name |
Glutamate carboxypeptidase 2 (FOLH1)
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Antigen Info | ||||
| Payload Name |
DM1
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
N-succinimidyl 4-(2-pyridyldithio) pentanoate (SPP)
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Linker Info | ||||
| Conjugate Type |
Random Lysines
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| Combination Type |
mertansine
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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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| Prostate cancer |
1 Trials
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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) | 52.4 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2.
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| Maximum Observed Concentration (Cmax) | 89.6 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2.
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[1] |
| Maximum Observed Concentration (Cmax) | 138.1 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2.
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| Maximum Observed Concentration (Cmax) | 214.9 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2.
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| Maximum Observed Concentration (Cmax) | 163.6 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2.
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| Maximum Observed Concentration (Cmax) | 273.3 | ug/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2.
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| Area Under the Concentration-Time Curve (AUC) | 2692 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 4858 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 9535 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 13210 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 10359 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 17658 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2, AUCinf.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 2692 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4858 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 9535 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 13210 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 10359 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 17658 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2, AUCinf.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 2692 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4858 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 9535 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 13210 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 10359 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 17658 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2, AUCinf.
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Excretion
| Standard Type | Value | Units | Description | Reference |
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| Elimination Half-Life (t1/2) | 55.7 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2.
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| Elimination Half-Life (t1/2) | 52.7 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2.
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| Elimination Half-Life (t1/2) | 59.2 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2.
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| Elimination Half-Life (t1/2) | 59.3 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2.
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| Elimination Half-Life (t1/2) | 59.9 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2.
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| Elimination Half-Life (t1/2) | 65.8 | h |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2692 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4858 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 9535 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 13210 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 10359 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2, AUCinf.
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| Area Under the Concentration-Time Curve (AUC) | 17658 | ug*h/mL |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2, AUCinf.
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| Clearance (CL) | 51.1 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 120 mg/m2.
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| Clearance (CL) | 35.6 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 168 mg/m2.
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| Clearance (CL) | 26.5 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 236 mg/m2.
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| Clearance (CL) | 26.1 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 2-week schedules, 330 mg/m2.
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| Clearance (CL) | 33.5 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 330 mg/m2.
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| Clearance (CL) | 26.8 | mL/h/m2 |
Mean pharmacokinetic parameters for all cycles of MLN2704 on 3-week schedules, 462 mg/m2.
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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] | ||||
| Patients Enrolled |
The study includes patients with histologically confirmed prostate adenocarcinoma showing progression via physical exam, imaging, or rising PSA despite castrate testosterone levels. Continuous LHRH analog therapy is required if initiated before screening, while prior anti-androgens require progression post-withdrawal. Effective barrier contraception is mandatory.
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| Administration Dosage |
Twenty-three patients received MLN2704 at doses of 18 to 343 mg/m2. Eighteen of these patients received ≥ three doses at 4-week intervals.
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| Related Clinical Trial | |||||
| NCT Number | NCT00052000 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1 Single Ascending Dose Trial of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen Independent Prostate Cancer | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Patients Enrolled |
Eligible patients require histologically confirmed metastatic prostate adenocarcinoma, age ≥18 years, disease progression despite castrate testosterone (<50 ng/dL), and continuous LHRH analog therapy unless surgically castrated. Key exclusions include testosterone >50 ng/dL, recent corticosteroids/chemotherapy, CNS metastases, neuropathy >Grade 2, abnormal labs (platelets <100K/mm <sup>3</sup>, ANC <1.5K/mm <sup>3</sup>, Hct <27%), active infections, severe cardiac/respiratory/renal/hepatic conditions, or limited life expectancy (<6 months).
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| Administration Dosage |
A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165 mg/m2; 12 patients); every 2 weeks (120, 168, 236, and 330 mg/m2; 15 patients); every 3 weeks (330 and 426 mg/m2; 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330 mg/m2; 17 patients).
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| Related Clinical Trial | |||||
| NCT Number | NCT00070837 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase 1/2 Dose Escalation Trial of Multiple Doses of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen-Independent Prostate Cancer | ||||
References