Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)
ADC ID
DRG0CRDKL
ADC Name
HKT-288
Synonyms
NOV-13; HKT 288; HKT288
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Organization
Novartis Pharma AG; Novartis AG
Drug Status
Terminated in phase 1
Indication
In total 5 Indication(s)
Epithelial ovarian cancer [ICD11:2B5D]
Terminated in phase 1
Fallopian tube cancer [ICD11:2C74]
Terminated in phase 1
Ovarian cancer [ICD11:2C73]
Terminated in phase 1
Peritoneal cancer [ICD11:2C51]
Terminated in phase 1
Renal cell carcinoma [ICD11:2C90]
Terminated in phase 1
Structure
Antibody Name
Fully human Anti-CDH6 HKT-288 mAb
  Antibody Info 
Antigen Name
Cadherin-6 (CDH6)
  Antigen Info 
Payload Name
Mertansine DM4
  Payload Info 
Therapeutic Target
Microtubule (MT)
  Target Info 
Linker Name
Sulfo-SPDB
  Linker Info 
Conjugate Type
Random conjugation through nucleophilic lysines.
Combination Type
Soravtansine
Puchem SID
472421193 , 404720140
ChEBI ID
CHEMBL4297979
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Click To Hide/Show 2 Activity Data Related to This Level
Standard Type NCT Number Clinical Status Clinical Trial Description
Undisclosed  NCT02947152
Phase 1
A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.

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Undisclosed  NCT02947152
Phase 1
A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.

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Discovered Using Cell Line-derived Xenograft Model
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Standard Type Value Units Cell Line Disease Model
Tumor Growth Inhibition value (TGI) 
≈ 90
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Tumor Growth Inhibition value (TGI) 
≈ 100
%
OVCAR-3 cells
Ovarian serous adenocarcinoma
Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
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Experiment 1 Reporting the Activity Date of This ADC [1]
Patients Enrolled
Advanced (metastatic or locally advanced) serous epithelial ovarian, serous fallopian tubal or serous primary peritoneal cancer or advanced clear cell or papillary renal cell carcinoma (RCC), who had received or were intolerant to all therapies known to confer clinical benefit for their disease and Eastern Cooperative Oncology Group (ECOG) performance status 2.

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Administration Dosage
HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.30 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly.
Related Clinical Trial
NCT Number NCT02947152  Clinical Status Phase 1
Clinical Description A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.
Primary Endpoint
The best overall response on the 0.30 mg/kg cohort in patients with measurable disease was RECIST v1.1 stable disease in 3 patients and PD in 2 patients.
Experiment 2 Reporting the Activity Date of This ADC [2]
Patients Enrolled
Patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.
Administration Dosage
Cadherin-6-targeting ADC iv at dose of 0.30, 0.75 mg/kg.
Related Clinical Trial
NCT Number NCT02947152  Clinical Status Phase 1
Clinical Description A phase 1, multicenter, open-label dose escalation and expansion study of HKT288, administered intravenously in adult patients with advanced solid tumors, including epithelial ovarian cancer and renal cell carcinoma.
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 2 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 90.00% (Day 45) High CDH6 expression (CDH6+++)
Method Description
CDH6-sulfo-DM4 induces efficient tumor cell killing in cell PDX models with CDH6 expression.
In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
Experiment 2 Reporting the Activity Date of This ADC [3]
Efficacy Data Tumor Growth Inhibition value (TGI) ≈ 100.00% (Day 45) High CDH6 expression (CDH6+++)
Method Description
CDH6-sulfo-DM4 induces efficient tumor cell killing in cell PDX models with CDH6 expression.
In Vivo Model Ovarian cancer CDX model
In Vitro Model Ovarian serous adenocarcinoma OVCAR-3 cells CVCL_0465
References
Ref 1 A Phase 1 Study of a CDH6-Targeting Antibody-Drug Conjugate in Patients with Advanced Solid Tumors with Evaluation of Inflammatory and Neurological Adverse Events. Oncol Res Treat. 2021;44(10):547-556.
Ref 2 A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of HKT288, Administered Intravenously in Adult Patients With Advanced Solid Tumors, Including Epithelial Ovarian Cancer and Renal Cell Carcinoma
Ref 3 Discovery and Optimization of HKT288, a Cadherin-6-Targeting ADC for the Treatment of Ovarian and Renal Cancers. Cancer Discov. 2017 Sep;7(9):1030-1045.

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