Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0XKZBO
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| ADC Name |
Puxitatug samrotecan
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| Synonyms |
puxitatug samrotecan; AZD8205; puxi-sam
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| Organization |
AstraZeneca (Top20 MNC) (Originator)
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| Drug Status |
Phase 3
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| Drug-to-Antibody Ratio |
8
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| Structure |
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| Antibody Name |
Puxitatug
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Antibody Info | ||||
| Antigen Name |
V-set domain-containing T-cell activation inhibitor 1 (VTCN1)
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Antigen Info | ||||
| Payload Name |
AZ14170132 (AZ0132)
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
Mal-PEG8-Val-Ala
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
samrotecan
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The indication landscape of This ADC(2027 Update)
The clinical trial pipeline of This ADC(2027 Update)
| Indication | Phase 1 | Phase 1/2 | Phase 2 | Phase 2/3 | Phase 3 | New Drug Application | Approved | ||||
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| Biliary tract cancer |
1 Trials
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| Breast cancer |
1 Trials
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| Endometrial cancer |
1 Trials
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1 Trials
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| Lung cancer |
1 Trials
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| Ovarian cancer |
1 Trials
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| Unspecific solid tumor |
1 Trials
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1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Absorption
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 136 | day*ug/mL |
Pharmacokinetic parameters of ADC in Tg32 mice, AUClast.
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| Maximum Observed Concentration (Cmax) | 93 | ug/mL |
Pharmacokinetic parameters of ADC in Tg32 mice.
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Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 136 | day*ug/mL |
Pharmacokinetic parameters of ADC in Tg32 mice, AUClast.
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| Volume of Distribution (Vd) | 143 | mL/kg |
Pharmacokinetic parameters of ADC in Tg32 mice.
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Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 136 | day*ug/mL |
Pharmacokinetic parameters of ADC in Tg32 mice, AUClast.
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Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 136 | day*ug/mL |
Pharmacokinetic parameters of ADC in Tg32 mice, AUClast.
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| Clearance (CL) | 34.1 | mL/day/kg |
Pharmacokinetic parameters of ADC in Tg32 mice.
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| Elimination Half-Life (t1/2) | 3.48 | day |
Pharmacokinetic parameters of ADC in Tg32 mice.
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General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
Discovered Using Patient-derived Xenograft Model
| Standard Type | Value | Units | Animal Model (No. of PDX) |
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| Objective Response Rate (ORR) |
69
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%
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Multiple tumor PDX model
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Full List of Activity Data of This Antibody-drug Conjugate
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
69%
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| Patients Enrolled |
Eligible patients (≥18 years) must have relapsed/metastatic solid tumors, measurable disease (RECIST 1.1), ECOG 0-1, and adequate organ function. Exclusions: active infections (HBV/HCV/HIV), untreated brain metastases, symptomatic cardiac disease (QTc >470 ms, heart failure, arrhythmias), recent anticancer therapy (<21 days for cytotoxic agents), or ILD. Sub-study-specific exclusions apply (e.g., autoimmune disorders for rilvegostomig combinations, CYP3A4 modifiers for saruparib).
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| Administration Dosage |
Single administration of 3.5 mg/kg AZD8205.
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| Related Clinical Trial | |||||
| NCT Number | NCT05123482 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (BLUESTAR) | ||||
| Primary Endpoint |
The study monitors safety parameters including adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and changes in lab values/ECGs/vital signs during treatment and up to 30 days post-dose. DLTs are assessed in Cycle 1 (21 days) per protocol-defined criteria.
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| Other Endpoint |
Efficacy is evaluated via RECIST 1.1, measuring objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), disease control rate at 12 weeks (DCR-12), and overall survival (OS). Pharmacokinetics (AUC, Cmax, Tmax, clearance, t1/2) and immunogenicity (ADA development) are assessed for AZD8205 alone or combined with rilvegostomig/saruparib. Intratumoral biomarkers (gamma H2AX) are analyzed in sub-studies.
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Patients 18 years old with cholangiocarcinoma, breast, ovarian or endometrial cancers and ECOG PS 0-1.
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| Administration Dosage |
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| 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
| Experiment 1 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Objective Response Rate (ORR) | 69% | 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.
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| In Vivo Model | Multiple tumor PDX model | ||||
References