Payload Information

General Information of This Payload
Payload ID
PAY0AQYPA
Name
DNA-damaging alkylating agent
Synonyms
DNA-damaging alkylating agent
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Target(s) Human Deoxyribonucleic acid (hDNA)
 Target Info 
The activity data of This Payload
Standard Type Value Units Cell line Disease Model Cell line ID Reference
Half Maximal Inhibitory Concentration (IC50) 0.000000002 M
NCI-H2110 cells
Lung non-small cell carcinoma
CVCL_1530 
[1]
Half Maximal Inhibitory Concentration (IC50) 0.000000003 M
T-47D cells
Invasive breast carcinoma
CVCL_0553 
[1]
Half Maximal Inhibitory Concentration (IC50) 0.000000005 M
KB cells
Human papillomavirus-related endocervical adenocarcinoma
CVCL_0372 
[1]
Each Antibody-drug Conjugate Related to This Payload
Full Information of The Activity Data of The ADC(s) Related to This Payload
TAK-164 [Phase 1]
 ADC Info 
Identified from the Human Clinical Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Date of This ADC [2]
Patients Enrolled
GCC-positive (H-score10 as indicated by IHC) GI cancers for whom standard treatment was no longer effective, or not available, Eligible GI malignancies included, but were not limited to: metastatic colorectal carcinoma, gastric carcinoma, esophageal carcinoma, small intestine cancer, and pancreatic cancer.
Administration Dosage
TAK-164 as a single intravenous infusion with a duration of up to 2 h, on day 1 of each 21-day cycle or every 3 weeks, until disease progression, unacceptable toxicity, or withdrawal from the study. Doses of 0.004 mg/kg, 0.008 mg/kg, 0.016 mg/kg, 0.032 mg/kg, 0.064 mg/kg, 0.12 mg/kg, 0.16 mg/kg, 0.19 mg/kg, 0.25 mg/kg, and 0.32 mg/kg were planned. To guide dose escalation, a method based on a Bayesian model of modified toxicity probability interval (mTPI) was used.

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Related Clinical Trial
NCT Number NCT03449030  Phase Status Phase 1
Clinical Description
An open-label, dose escalation, phase 1, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C.
Primary Endpoint
Dosing was capped at 0.19 mg/kg due to hepatic toxicity. The RP2D was determined as 0.064 mg/kg but was considered insufficient to derive significant clinical benefit.
Other Endpoint
No pts had dose-limiting toxicities (DLT) in cycle 1 up to 0.32 mg/kg. TAK-164 appeared to have a manageable safety profile up to 0.064 mg/kg in pts with advanced GI cancers.
References
Ref 1 Site-Specific Conjugation of the Indolinobenzodiazepine DGN549 to Antibodies Affords Antibody-Drug Conjugates with an Improved Therapeutic Index as Compared with Lysine Conjugation. Bioconjug Chem. 2020 Jan 15;31(1):93-103.
Ref 2 A phase I, first-in-human study of TAK-164, an antibody-drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C. Cancer Chemother Pharmacol. 2023 Apr;91(4):291-300.

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