Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0WRFYU
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| ADC Name |
PF-06650808
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| Synonyms |
PF-06650808
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| Organization |
Pfizer (Top20 MNC) (Originator)
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| Drug Status |
Phase 1 (discontinued)
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| Drug-to-Antibody Ratio |
4
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| Structure |
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| Antibody Name |
Hu28
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Antibody Info | Antigen Name | |||
| Payload Name |
Auristatin 0101 (Aur0101)
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
pelidotin
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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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| Breast cancer |
1 Trials
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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) | 5.245 | ug/mL |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 0.967 | h |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 126.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 9.515 | ug/mL |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 0.974 | h |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 310.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 18.75 | ug/mL |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 0.967 | h |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 537 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 34.75 | ug/mL |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 1.01 | h |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 62.2 | ug/mL |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 0.967 | h |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1773 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 56.2 | ug/mL |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 1.03 | h |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2205 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 78.67 | ug/mL |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 1.06 | h |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3736 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 75.28 | ug/mL |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 1.04 | h |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3103 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg, AUCinf.
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[1] |
| Maximum Observed Concentration (Cmax) | 116.6 | ug/mL |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg.
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[1] |
| Time to Maximum Concentration (Tmax) | 1.45 | h |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg, AUCinf.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 126.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.44 | L |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 310.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 2.79 | L |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 537 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 2.855 | L |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.6 | L |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1773 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.513 | L |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2205 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.35 | L |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3736 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.928 | L |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3103 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 3.66 | L |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg, AUCinf.
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[1] |
| Volume of Distribution (Vd) | 5.04 | L |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg.
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 126.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 310.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 537 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1773 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2205 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3736 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3103 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg, AUCinf.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg, AUCinf.
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 126.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 18.6 | h |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg.
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[1] |
| Clearance (CL) | 0.1305 | L/h |
Pharmacokinetic parameters for PF-06650808 0.2 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 310.5 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 24.2 | h |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg.
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[1] |
| Clearance (CL) | 0.0803 | L/h |
Pharmacokinetic parameters for PF-06650808 0.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 537 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 21.05 | h |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg.
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[1] |
| Clearance (CL) | 0.08815 | L/h |
Pharmacokinetic parameters for PF-06650808 0.8 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 23.65 | h |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg.
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[1] |
| Clearance (CL) | 0.1067 | L/h |
Pharmacokinetic parameters for PF-06650808 1.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1773 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 29.52 | h |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg.
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[1] |
| Clearance (CL) | 0.08585 | L/h |
Pharmacokinetic parameters for PF-06650808 2.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2205 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 30.72 | h |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg.
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[1] |
| Clearance (CL) | 0.07766 | L/h |
Pharmacokinetic parameters for PF-06650808 2.4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3736 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 35.12 | h |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg.
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[1] |
| Clearance (CL) | 0.0819 | L/h |
Pharmacokinetic parameters for PF-06650808 3.0 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 3103 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 32.72 | h |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg.
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[1] |
| Clearance (CL) | 0.07914 | L/h |
Pharmacokinetic parameters for PF-06650808 3.6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 4170 | ug*h/mL |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg, AUCinf.
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[1] |
| Elimination Half-Life (t1/2) | 40.8 | h |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg.
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[1] |
| Clearance (CL) | 0.0947 | L/h |
Pharmacokinetic parameters for PF-06650808 4.68 mg/kg.
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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] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
9.68
16.67 21.43 % |
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| Patients Enrolled |
Locally advanced/metastatic solid tumors resistant to standard therapy or with no available standard therapy; Eastern Cooperative Oncology Group (ECOG) performance score (PS) 01; a life expectancy 12 weeks; and adequate bone marrow, hepatic, and renal function.
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| Administration Dosage |
Intravenously every 3 weeks (Q3W) starting at a dose of 0.20 mg/kg to be escalated up to 6.40 mg/kg, following the modified continual reassessment method (mCRM).
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| Related Clinical Trial | |||||
| NCT Number | NCT02129205 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 dose escalation study evaluating the safety and tolerability of PF-06650808 In patients with advanced solid tumors. | ||||
| Primary Endpoint |
OrR=9.68% for all response-evaluable patients (N=3/31), ORR=16.67% for patients with breast cancer (N=3/18), ORR=21.43% for patients with ER+ breast cancer (N=3/14). Five patients with advanced BC achieved PR as best overall response (BOR): 2 at 2.0 mg/kg, 1 at 2.4 mg/kg, and 2 at 3.6 mg/kg.
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| Other Endpoint |
The maximum tolerated dose (MTD) was estimated to be 2.40 mg/kg.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT02129205 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 dose escalation study evaluating the safety and tolerability of PF-06650808 in patients with advanced solid tumors. | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Inclusion requires advanced/metastatic solid tumors resistant to standard therapy or TNBC with Notch3 expression, measurable lesions, and organ function. Exclusion includes recent surgery/radiation (4 weeks), symptomatic brain metastases needing steroids, or prior same-mechanism treatment.
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| Administration Dosage |
Dose Escalation Phase [Part 1] - PF-06650808 will be administered at doses starting at 0.2 mg/kg. Increases in dose will continue until MTD is determined.Dose Expansion Phase [Part 2] - Patients will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.
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| Related Clinical Trial | |||||
| NCT Number | NCT02129205 | Clinical Status | PHASE1 | ||
| Clinical Description | A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS | ||||
| Primary Endpoint |
This section defines Dose-limiting Toxicities (DLT) assessed during Part 1 over 21 days, categorized into hematologic (Grade 4 neutropenia >7 days, febrile neutropenia, thrombocytopenia with bleeding) and non-hematologic (Grade ≥3 toxicities, treatment delays >2 weeks). It also outlines Objective Response criteria (complete/partial response) based on RECIST v1.1 for Part 1 and 2, covering target/non-target lesion assessments every 6 weeks until progression or 3 years.
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| Other Endpoint |
This segment details Treatment-Emergent Adverse Events (TEAEs) over 3 years, including serious AEs (death, hospitalization, disability), lab abnormalities (hematology, chemistry, urinalysis), and vital signs criteria (BP, pulse rate). Pharmacokinetic parameters (Cmax, Tmax, AUCtau, CL, Vss, t1/2) for ADC components are provided, along with anti-drug antibody (ADA) testing and survival metrics (PFS, OS) for Part 2.
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References