Linker Information
General Information of This Linker
| Linker ID |
LIN0EBCCY
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| Linker Name |
K-lock-Val-Cit-PABC
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| Linker Type |
Site-specific conjugation linker; Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C28H42N6O8
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| Isosmiles |
CC(C)C(NC(=O)CCC(=O)N1CCC(C(=O)O)CC1)C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(CO)cc1
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| InChI |
InChI=1S/C28H42N6O8/c1-17(2)24(33-22(36)9-10-23(37)34-14-11-19(12-15-34)27(40)41)26(39)32-21(4-3-13-30-28(29)42)25(38)31-20-7-5-18(16-35)6-8-20/h5-8,17,19,21,24,35H,3-4,9-16H2,1-2H3,(H,31,38)(H,32,39)(H,33,36)(H,40,41)(H3,29,30,42)
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| InChIKey |
JEAVOUQZXPLKLO-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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590.678
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Polar area
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220.26
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Complexity
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42
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xlogp Value
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0.2949
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Heavy Count
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42
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Rot Bonds
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15
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Hbond acc
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7
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Hbond Donor
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7
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Trastuzumab botidotin [Approved in 2025]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| 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.
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| 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 | [2] | ||||
| 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).
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| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| 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.
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| Experiment 4 Reporting the Activity Date of This ADC | [4] | ||||
| 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.
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| Experiment 5 Reporting the Activity Date of This ADC | [5] | ||||
| 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
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| 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 | [5] | ||||
| 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
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| 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 | [5] | ||||
| 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
|
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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 8 Reporting the Activity Date of This ADC | [5] | ||||
| 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
|
||||
| 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
|
||||
| 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.
|
||||
| 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 | [6] | ||||
| 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)
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| 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 | [7] | ||||
| 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.
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| Administration Dosage |
4.8 mg/kg for each 21 day cycle
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| 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
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| 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.
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| 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.
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References