Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0XKZBO
ADC Name	AZD-8205
Synonyms	AZD 8205; AZD-8205; AZD8205 Click to Show/Hide
Organization	AstraZeneca PLC; BSP Pharmaceuticals SpA
Drug Status	Phase 1/2
Indication	In total 4 Indication(s) Cholangiocarcinoma [ICD11:2C12] Phase 2 Ovarian cancer [ICD11:2C73] Phase 2 Solid tumors [ICD11:2A00-2A0Z\|2B50-2F9Z] Phase 2 Triple negative breast cancer [ICD11:2C60-2C65] Phase 2
Drug-to-Antibody Ratio	8
Structure
	3D MOL	2D MOL
Antibody Name	INT016		Antibody Info
Antigen Name	V-set domain-containing T-cell activation inhibitor 1 (VTCN1)		Antigen Info
Payload Name	Topoisomerase I inhibitor		Payload Info
Therapeutic Target	DNA topoisomerase 1 (TOP1)		Target Info
Linker Name	Mal-PEG8-Val-Ala		Linker Info
Conjugate Type	Random conjugation through reduced inter-chain cysteines.
Combination Type	AZ0133

General Information of The Activity Data Related to This ADC

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT05123482	Phase 1/2	A phase 1/2a multi-center, open-label master protocol to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AZD8205 in participants with advanced or metastatic solid malignancies. Click to Show/Hide

Discovered Using Patient-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Standard Type	Value	Units	Animal Model (No. of PDX)
Objective Response Rate (ORR)	69	%	Multiple tumor PDX model

Full List of Activity Data of This Antibody-drug Conjugate

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	Patients 18 years old with cholangiocarcinoma, breast, ovarian or endometrial cancers and ECOG PS 0-1.
Administration Dosage	.
*Related Clinical Trial*
NCT Number	NCT05123482	Clinical Status	Phase 1/2
Clinical Description	A phase 1/2a multi-center, open-label master protocol to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of AZD8205 in participants with advanced or metastatic solid malignancies.

Discovered Using Patient-derived Xenograft Model

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Objective Response Rate (ORR)	69.00%	Positive VTCN1 expression (VTCN1+++/++)
Method Description	In the study of 26 PDX tumors,single administration of 3.5 mg/kg AZD8205 to determine the ORR,according to modified RECIST criteria,which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models.
In Vivo Model	Multiple tumor PDX model

References

Ref 1	First in human dose-escalation trial with the c-MET targeting antibody-drug conjugate BYON3521. Cancer Res (2023) 83 (8_Supplement): CT185.
Ref 2	Design and Preclinical Evaluation of a Novel B7-H4-Directed Antibody-Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305. Clin Cancer Res. 2023 Mar 14;29(6):1086-1101.