Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0UIDCY
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| ADC Name |
NJH395
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| Synonyms |
NJH395
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| Organization |
Novartis (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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| Antibody Name |
MIW338
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Antibody Info | ||||
| Antigen Name |
Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)
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Antigen Info | ||||
| Payload Name |
TLR7 agonist
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Payload Info | ||||
| Therapeutic Target |
Toll-like receptor 7 (TLR7)
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Target Info | ||||
| Linker Name |
A non-cleavable linker
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Linker Info | ||||
| Conjugate Type |
Reactive Cysteines
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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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| 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) | 0.8 | ug/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.1 mg/kg, N=4.
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[1] |
| Time to Maximum Concentration (Tmax) | 7.3 | h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.1 mg/kg, N=4.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 173.7 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.2 mg/kg, N=3.
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| Maximum Observed Concentration (Cmax) | 3.4 | ug/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.2 mg/kg, N=3.
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| Time to Maximum Concentration (Tmax) | 1.6 | h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.2 mg/kg, N=3.
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| Area Under the Concentration-Time Curve (AUC) | 298.6 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.4 mg/kg, N=4.
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| Maximum Observed Concentration (Cmax) | 6.6 | ug/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.4 mg/kg, N=4.
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| Time to Maximum Concentration (Tmax) | 5.8 | h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.4 mg/kg, N=4.
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| Area Under the Concentration-Time Curve (AUC) | 971.2 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.8 mg/kg, N=3.
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| Maximum Observed Concentration (Cmax) | 18.7 | ug/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.8 mg/kg, N=3.
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| Time to Maximum Concentration (Tmax) | 1.6 | h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.8 mg/kg, N=3.
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| Area Under the Concentration-Time Curve (AUC) | 2141.5 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 1.6 mg/kg, N=4.
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| Maximum Observed Concentration (Cmax) | 27.7 | ug/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 1.6 mg/kg, N=4.
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| Time to Maximum Concentration (Tmax) | 1.7 | h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 1.6 mg/kg, N=4.
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 173.7 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.2 mg/kg, N=3.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 298.6 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.4 mg/kg, N=4.
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| Area Under the Concentration-Time Curve (AUC) | 971.2 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.8 mg/kg, N=3.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2141.5 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 1.6 mg/kg, N=4.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 173.7 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.2 mg/kg, N=3.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 298.6 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.4 mg/kg, N=4.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 971.2 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.8 mg/kg, N=3.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2141.5 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 1.6 mg/kg, N=4.
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 173.7 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.2 mg/kg, N=3.
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| Clearance (CL) | 79.2 | mL/h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.2 mg/kg, N=3.
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| Area Under the Concentration-Time Curve (AUC) | 298.6 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.4 mg/kg, N=4.
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| Clearance (CL) | 74.9 | mL/h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.4 mg/kg, N=4.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 971.2 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 0.8 mg/kg, N=3.
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| Clearance (CL) | 55.5 | mL/h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 0.8 mg/kg, N=3.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 2141.5 | ug*h/mL |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, AUCinf, 1.6 mg/kg, N=4.
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| Clearance (CL) | 49.2 | mL/h |
Mean pharmacokinetic parameters in plasma from patients with HER2-positive advanced malignancies treated with NJH395, 1.6 mg/kg, N=4.
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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 |
Eligible patients must have HER2+ non-breast solid tumors refractory to standard therapies (ECOG ≤2) with biopsy-accessible lesions. Key exclusions include prior TLR7/8 treatment, cardiac dysfunction, autoimmune/active lung diseases, HIV, checkpoint inhibitor toxicity history, or QT-prolonging drug use. Additional protocol criteria may apply.
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| Administration Dosage |
As of July 01, 2020, 18 patients (10 males, 8 females; median age, 52.5 years [range, 42-74 years]) were enrolled in 5 dose cohorts (0.1-1.6 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT03696771 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I, Multicenter, Open-label Dose Finding Study of NJH395, Administered Intravenously in Patients With Non-breast HER2+ Advanced Malignancies | ||||
| Primary Endpoint |
Dose-limiting toxicities (DLTs) incidence and severity will be assessed over 21 days, extending to 42 days in the second study phase. Adverse event data collection spans 2.5 years.
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| Other Endpoint |
PK profiles for NJH395 and metabolites will be tracked for 126 days, including Cmax/AUC measurements. Anti-drug antibody assessment and efficacy endpoints (ORR, CBR, PFS, DOR per RECIST v1.1/iRECIST) will be evaluated over 2.5 years. Tumor infiltrating lymphocyte changes will be monitored via IHC at specified treatment cycles (21-day intervals).
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
0%
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| Patients Enrolled |
Patients with nonbreast HER2+ advanced malignancies.
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| Administration Dosage |
5 dose cohorts (0.10-1.60 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT03696771 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1, multicenter, open-label dose finding study of NJH395, administered intravenously in patients with non-breast HER2+ advanced malignancies. | ||||
References