Payload Information

General Information of This Payload
Payload ID
PAY0KFOXJ
Name
DGN549
Synonyms
DGN549
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Target(s) Human Deoxyribonucleic acid (hDNA)
 Target Info 
Structure
Formula
C41H35N5O6
Isosmiles
COc1cc2c(cc1OCc1cc(N)cc(COc3cc4nc5n(c(=O)c4cc3OC)-c3ccccc3C5)c1)NCC1Cc3ccccc3N1C2=O
InChI
InChI=1S/C41H35N5O6/c1-49-35-16-29-31(43-20-28-14-25-7-3-5-9-33(25)45(28)40(29)47)18-37(35)51-21-23-11-24(13-27(42)12-23)22-52-38-19-32-30(17-36(38)50-2)41(48)46-34-10-6-4-8-26(34)15-39(46)44-32/h3-13,16-19,28,43H,14-15,20-22,42H2,1-2H3
InChIKey
OUWGFOQJFNYLSZ-UHFFFAOYSA-N
Pharmaceutical Properties
Molecule Weight
693.76
Polar area
130.17
Complexity
693.2587338
xlogp Value
6.0443
Heavy Count
52
Rot Bonds
8
Hbond acc
10
Hbond Donor
2
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 (Terminated)]
 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 [1]
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 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.