Linker Information

General Information of This Linker
Linker ID
LIN0EBCCY
Linker Name
K-lock-Val-Cit-PABC
Linker Type
Site-specific conjugation linker; Cathepsin-cleavable linker
Antibody-Linker Relation
Cleavable
Structure
Formula
C28H42N6O8
Isosmiles
CC(C)C(NC(=O)CCC(=O)N1CCC(C(=O)O)CC1)C(=O)NC(CCCNC(N)=O)C(=O)Nc1ccc(CO)cc1
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)
InChIKey
JEAVOUQZXPLKLO-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
590.678
Polar area
220.26
Complexity
42
xlogp Value
0.2949
Heavy Count
42
Rot Bonds
15
Hbond acc
7
Hbond Donor
7
Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
A-166 [NDA]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 4 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [1]
Efficacy Data Partial Response (PR)
25.92%
Patients Enrolled
Locally advanced/metastatic solid tumors expressing human epidermal growth factor receptor 2 (HER2) or are HER2 amplified.
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.
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%.

   Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC [2]
Efficacy Data Objective Response Rate (ORR)
73.90% (4.8 mg/kg)
68.60% (6.0 mg/kg)
Patients Enrolled
Patients with HER2-expressing advanced solid tumours.
Administration Dosage
0.10, 0.30, 0.60, 1.20, 2.40, 3.60, 4.80 or 6.00 mg/kg Q3W.
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 [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.
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.
References
Ref 1 A first in-human study of A166 in patients with locally advanced/metastatic solid tumors which are HER2-positive or HER2-amplified who did not respond or stopped responding to approved therapies. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 1049-1049.
Ref 2 Phase I study of A166, an antibodydrug conjugate in advanced HER2-expressing solid tumours. NPJ Breast Cancer. 2023 Apr 18;9(1):28. doi: 10.1038/s41523-023-00522-5.
Ref 3 An Open-clinical Trial Phase , Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast CancerKL166-IIS-001, NCT05346328
Ref 4 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, NCT03602079

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