Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0PZSXJ
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| ADC Name |
Trastuzumab botidotin
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| Synonyms |
trastuzumab botidotin; A166; KL-A166
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| Organization |
Levena Biopharma (Originator);Kelun Biotherapeutics
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| Drug Status |
Approved in 2025
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| Drug-to-Antibody Ratio |
2
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| Structure |
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| Antibody Name |
Trastuzumab
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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 |
Duostatin 5
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
K-lock-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Reactive Lysines
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| Combination Type |
botidotin
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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 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Breast cancer |
1 Trials
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4 Trials
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1 Trials
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| Gastric cancer |
1 Trials
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| Gastroesophageal junction adenocarcinoma |
1 Trials
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| Lung cancer |
1 Trials
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| Unspecific solid tumor |
1 Trials
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1 Trials
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| Urothelial cancer |
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) | 4.51 | ug/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 279 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 283 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 8.65 | ug/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 679 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 682 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 20.7 | ug/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1870 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1890 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 40.9 | ug/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6390 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 60.8 | ug/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 12400 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 15000 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 92.5 | ug/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 18100 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22800 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUCinf
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[1] |
| Maximum Observed Concentration (Cmax) | 109 | ug/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22200 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUCinf
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 279 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 283 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3660 | mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 679 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 682 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3160 | mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1870 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1890 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3620 | mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6390 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3110 | mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 12400 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 15000 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3430 | mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 18100 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22800 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3960 | mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22200 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUCinf
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[1] |
| Volume of Distribution (Vd) | 3720 | mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 279 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 283 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 679 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 682 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1870 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1890 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6390 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 12400 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 15000 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 18100 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22800 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUCinf
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22200 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUCinf
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 279 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 283 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 1.65 | day |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1
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[1] |
| Clearance (CL) | 64 | mL/h |
Pharmacokinetic properties of A166 ADC, 0.3 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 679 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 682 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1, AUCinf
|
[1] |
| Elimination Half-Life (t1/2) | 2.06 | day |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1
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[1] |
| Clearance (CL) | 44.4 | mL/h |
Pharmacokinetic properties of A166 ADC, 0.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1870 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 1890 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 2.41 | day |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1
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[1] |
| Clearance (CL) | 43.4 | mL/h |
Pharmacokinetic properties of A166 ADC, 1.2 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6390 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 6600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 3.68 | day |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1
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[1] |
| Clearance (CL) | 24.4 | mL/h |
Pharmacokinetic properties of A166 ADC, 2.4 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 12400 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 15000 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 7.75 | day |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1
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[1] |
| Clearance (CL) | 12.8 | mL/h |
Pharmacokinetic properties of A166 ADC, 3.6 mg/kg, n=3, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 18100 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22800 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 8.83 | day |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1
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[1] |
| Clearance (CL) | 12.9 | mL/h |
Pharmacokinetic properties of A166 ADC, 4.8 mg/kg, n=27, Cycle 1
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 22200 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUClast
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 26600 | ug*h/mL |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1, AUCinf
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[1] |
| Elimination Half-Life (t1/2) | 8.33 | day |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1
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[1] |
| Clearance (CL) | 12.9 | mL/h |
Pharmacokinetic properties of A166 ADC, 6.0 mg/kg, n=38, Cycle 1
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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 | Partial Response (PR) |
25.92%
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| Patients Enrolled |
Locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified.
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| Administration Dosage |
0.30, 1.20, 3.60, 4.80 mg/kg, every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.
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| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1-2, FIH Study of A166 in locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified that did not respond or stopped responding to approved therapies. | ||||
| Primary Endpoint |
Overall incidence of ophthalmic toxicities in the 3.60 mg/kg cohort was 80% and in the 4.80 mg/kg cohort it was 83.00%. Responses were seen only at the dose levels of 3.60 mg/kg and 4.80 mg/kg. Among the 27 patients evaluable for efficacy,best response was progression of disease in 11 patients (40.74%), stable disease in 9 patients (33.33%) and partial response in 7 patients (25.92%),for the total disease control rate of 59%.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
73.90
68.60 % |
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| Patients Enrolled |
Patients with HER2-expressing advanced solid tumours.
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| Administration Dosage |
0.10, 0.30, 0.60, 1.20, 2.40, 3.60, 4.80 or 6.00 mg/kg Q3W.
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| Related Clinical Trial | |||||
| NCT Number | NCT05311397 | Clinical Status | Phase 1 | ||
| Clinical Description | A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of A166 in patients with unresectable, locally advanced or metastatic HER2-expressing solid tumors (KL166-I-01-CTP). | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05346328 | Clinical Status | Phase 2 | ||
| Clinical Description | An open-clinical trial phase , injection of A166 for HER2-positive patients with refractory unresectable locally advanced or metastatic breast cancer KL166-2S-001. | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [5] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | Phase 1/2 | ||
| Clinical Description | A phase 1-2, FIH study of A166 in locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified that did not respond or stopped responding to approved therapies. | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | stable disease (SD) |
33%
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| Patients Enrolled |
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.
Click to Show/Hide
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| Administration Dosage |
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
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| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies | ||||
| Primary Endpoint |
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
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| Other Endpoint |
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
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| Experiment 6 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | progressive disease (PD) |
41%
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| Patients Enrolled |
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.
Click to Show/Hide
|
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| Administration Dosage |
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
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| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies | ||||
| Primary Endpoint |
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
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| Other Endpoint |
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
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| Experiment 7 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Partial Response (PR) |
26%
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| Patients Enrolled |
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.
Click to Show/Hide
|
||||
| Administration Dosage |
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
|
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| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies | ||||
| Primary Endpoint |
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
|
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| Other Endpoint |
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
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| Experiment 8 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Disease control rate (DCR) |
59%
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| Patients Enrolled |
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) malignancies who exhausted standard therapies, with adequate hematologic/organ function (ANC≥1500/uL, CrCl≥50mL/min, LVEF≥45%), excluding those with cardiac dysfunction (NYHA III-IV, QTc>470ms), active hepatitis/HIV, uncontrolled comorbidities, prior trastuzumab intolerance, or symptomatic brain metastases. Fertile patients must use contraception for 7 months post-treatment.
Click to Show/Hide
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| Administration Dosage |
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
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| Related Clinical Trial | |||||
| NCT Number | NCT03602079 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies | ||||
| Primary Endpoint |
The phase I primary endpoint evaluates maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) in HER2-positive advanced cancer patients over a 21-day DLT observation period, with continuous safety monitoring up to 24 months.
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| Other Endpoint |
Secondary phase I objectives include comprehensive safety assessment (CTCAE v4.03 graded AEs, immunogenicity via anti-drug antibodies) and pharmacokinetic profiling (Cmax, CL, AUC, hale-life, Vz, Vss) through 84-day PK sampling in this dose-escalation study.
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| Experiment 9 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Eligibility requires adults (≥18) with incurable HER2+ (IHC≥1+/ISH/NGS-confirmed) solid tumors who have exhausted standard therapies, with adequate organ function and ECOG 0-1.
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| Administration Dosage |
According to the initial dose, the highest dose and the modified Fibonacci method, the dose escalation of A166 for injection is designed as: 0.1 mg/kg, 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg (the highest dose is tentatively set at 4.8 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT05311397 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of A166 in Patients With Unresectable, Locally Advanced or Metastatic HER2-expressing Solid Tumors (KL166-I-01-CTP) | ||||
| Primary Endpoint |
Primary endpoint evaluates investigator-assessed ORR (CR+PR) per RECIST v1.1 criteria in HER2-positive advanced solid tumor patients over 24 months.
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| Other Endpoint |
Secondary endpoints include 24-month assessments of DOR (from first response to PD/death), PFS (from randomization to PD/death), and OS (from randomization to death/loss to follow-up), all measured according to RECIST v1.1 standards.
|
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| Experiment 10 Reporting the Activity Date of This ADC | [8] | ||||
| Patients Enrolled |
Eligibility includes adults (18-75y) with confirmed HER2+ (IHC3+ or IHC2+/FISH+) metastatic breast cancer and prior taxane exposure, excluding those with cardiac dysfunction (NYHA III-IV/QTc prolongation), active ILD, uncontrolled CNS metastases, or trastuzumab intolerance, while requiring adequate organ function for safety evaluation.
|
||||
| Administration Dosage |
4.8 mg/kg for each 21 day cycle
|
||||
| Related Clinical Trial | |||||
| NCT Number | NCT05346328 | Clinical Status | PHASE2 | ||
| Clinical Description | An Open-clinical Trial Phase II, Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast Cancer;KL166-IIS-001 | ||||
| Primary Endpoint |
The primary endpoint evaluates ORR (complete/partial response rates per RECIST 1.1) in HER2-positive metastatic breast cancer patients over 24 months, focusing on heavily pretreated populations who failed ≥3 prior HER2-targeted therapies including trastuzumab, TKIs, and ADCs.
|
||||
| Other Endpoint |
Secondary objectives assess 24-month efficacy through PFS (first dose to progression/death), DCR/CRB (response+stable disease), DOR (response duration), TTR (time to progression excluding deaths), and OS (overall survival from first dose), all measured by RECIST 1.1 standards in this refractory patient population.
|
||||
References