Linker Information
General Information of This Linker
| Linker ID |
LIN0KDRVI
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| Linker Name |
Mal-PEG8-Val-Ala
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| Linker Type |
Cathepsin-cleavable linker
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| Antibody-Linker Relation |
Cleavable
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| Structure |
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| Formula |
C34H58N4O15
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| Isosmiles |
CC(NC(=O)C(NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O)C(C)C)C(=O)O
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| InChI |
InChI=1S/C34H58N4O15/c1-26(2)32(33(43)36-27(3)34(44)45)37-29(40)7-10-46-12-14-48-16-18-50-20-22-52-24-25-53-23-21-51-19-17-49-15-13-47-11-8-35-28(39)6-9-38-30(41)4-5-31(38)42/h4-5,26-27,32H,6-25H2,1-3H3,(H,35,39)(H,36,43)(H,37,40)(H,44,45)
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| InChIKey |
GITGYODHQZKNBP-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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762.851
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Polar area
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235.82
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Complexity
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53
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xlogp Value
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-1.3293
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Heavy Count
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53
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Rot Bonds
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35
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Hbond acc
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14
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Hbond Donor
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4
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Each Antibody-drug Conjugate Related to This Linker
Full Information of The Activity Data of The ADC(s) Related to This Linker
Puxitatug samrotecan [Phase 3]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| 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)
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| 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 | [4] | ||||
| Patients Enrolled |
Patients 18 years old with cholangiocarcinoma, breast, ovarian or endometrial cancers and ECOG PS 0-1.
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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.
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Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [6] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
69%
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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 | ||||
Lixarkitug samrotecan [Phase 1/2 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [2] | ||||
| Patients Enrolled |
Key eligibility: Adults (≥18) with CD123+ R/R AML or HR-MDS (≥5% blasts) after ≥1 prior therapy, ECOG ≤2. Major exclusions: CNS leukemia, prior CD123-targeted therapy, recent HSCT/cell therapy (90/60 days), active GVHD requiring immunosuppression, uncontrolled infections, or unresolved Grade ≥2 AEs from prior treatments.
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| Administration Dosage |
AZD9829 will be administered by IV infusion
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| Related Clinical Trial | |||||
| NCT Number | NCT06179511 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Modular Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD9829 as Monotherapy or in Combination in Patients With CD123-Positive Hematological Malignancies
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| Primary Endpoint |
Primary endpoints include DLT frequency assessment (28-day observation) and comprehensive safety evaluation (CTCAE v4.0) of AZD9829 in R/R AML patients, monitoring AEs/SAEs from consent until 60 days post-treatment to determine RP2D based on safety and PK profiles.
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| Other Endpoint |
Secondary objectives comprise detailed PK analysis (plasma concentrations, AUC, Cmax, tmax, clearance, t1/2) and immunogenicity (ADA incidence) measured up to 30 days post-dose, along with efficacy outcomes (ORR, CCRR, CR/CRi per ELN2022/IWG criteria, DoR, TTR, TTNT, PFS, OS, EFS) assessed over 1 year.
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Torvutatug samrotecan [Phase 3]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Patients Enrolled |
Eligible participants ≥18 years have advanced solid tumors, measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Exclusions: uncontrolled infections (HBV/HCV/HIV), active ILD, significant cardiac disease (QTc >470 ms, heart failure), recent cancer (except cured malignancies), or pregnancy. Contraception is mandated. Prior therapies must meet washout criteria.
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| Administration Dosage |
Pts aged ≥18 years with PRROC were recruited irrespective of tumour FRalpha expression and without a limit on the number of prior lines of therapy. AZD5335 was administered intravenously Q3W until disease progression, unacceptable toxicity, or other reason for discontinuation.
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| Related Clinical Trial | |||||
| NCT Number | NCT05797168 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description |
A Modular Phase I/IIa, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors
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| Primary Endpoint |
The study assesses the safety and tolerability of AZD5335/AZD5305 by monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) per NCI CTCAE v5.0, including lab abnormalities, vital signs, and ECGs.
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| Other Endpoint |
Efficacy is evaluated via RECIST v1.1, measuring ORR (CR/PR), DCR (CR/PR/SD ≥15 weeks), DoR, PFS, and OS. PK parameters (AUC, Cmax, Tmax, clearance, t1/2) are analyzed for AZD5335 alone or combined with AZD5305/bevacizumab/carboplatin. Immunogenicity (ADA development) and tumor target expression changes are also assessed.
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| Experiment 2 Reporting the Activity Date of This ADC | [5] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT05797168 | Clinical Status | Phase 1/2 | ||
| Clinical Description |
FONTANA: A modular phase 1/2a, open-label, multi-center study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ascending doses of AZD5335 monotherapy and in combination with anti-cancer agents in participants with solid tumors.
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| Primary Endpoint |
Number of participants with adverse events/serious adverse events, the number of participants with dose limiting toxicity (DLT).
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| Other Endpoint |
Objective Response Rate (ORR), Duration of Response (DoR), Disease Control Rate (DCR), Progression free Survival (PFS), Overall Survival (OS).
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Tilatamig samrotecan [Phase 2]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [7] | ||||
| Patients Enrolled |
Eligible patients (≥18 years, ECOG 0-1) require measurable disease (RECIST v1.1), adequate organ function, and module-specific histology confirmation (EGFRmut NSCLC/HNSCC/CRC). Key exclusions include active ILD, untreated CNS metastases, uncontrolled infections, or significant cardiac comorbidities.
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| Related Clinical Trial | |||||
| NCT Number | NCT05647122 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase I, Multicenter, Open-label, First-in-Human, Dose Escalation and Expansion Study of AZD9592 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumors
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| Primary Endpoint |
Primary endpoints include AE/SAE incidence (monitored from consent to 30 days post-treatment), DLT assessment during first 21 days, lab/ECG/vital sign changes, and ORR (RECIST v1.1) in expansion cohorts over ~2 years.
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| Other Endpoint |
Secondary endpoints comprise efficacy measures (ORR/DOR/DCR/PFS/OS) assessed via RECIST v1.1 over ~2 years, comprehensive PK analysis (AUC/Cmax/Tmax/clearance/half-life), and ADA immunogenicity evaluation until 30 days post-treatment.
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| Experiment 2 Reporting the Activity Date of This ADC | [8] | ||||
| Patients Enrolled |
Eligible patients (≥18 years, ECOG 0-2) require confirmed HNSCC (oropharynx/hypopharynx/oral cavity/larynx) with injectable lesions meeting viability criteria. Key exclusions: insufficient tumor volume, critical structure proximity, prior immune/ADC therapy (last 5 years), pregnancy/lactation, uncontrolled comorbidities, or recent major surgery (<4 weeks). Contraception required for 7 months post-procedure.
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| Related Clinical Trial | |||||
| NCT Number | NCT06366451 | Clinical Status | EARLY_PHASE1 | ||
| Clinical Description |
A Phase 0 Multicenter Study of the Pharmacodynamic Effects of Intratumoral Microdose Administration of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592
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| Primary Endpoint |
The primary objective involves spatial transcriptomic analysis (NanoString GeoMx DSP) of tumor microenvironments 1-3 days post-microdose injection of rilvegostomig, volrustomig, sabestomig, AZD9592, or pembrolizumab (mono/combination therapy), evaluating 1800+ genes with potential IHC/ISH validation.
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| Other Endpoint |
Safety monitoring includes AE/ADE assessment (frequency, severity, causality) for 28 days post-microdose procedure in HNSCC patients with surgically accessible lesions (primary/recurrent/metastatic).
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| Experiment 3 Reporting the Activity Date of This ADC | [9] | ||||
| Patients Enrolled |
Patients with metastatic non-small cell lung cancer (mNSCLC) with EGFRm (sensitizing L858R mutation or exon 19 deletions) or EGFR wild-type, or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
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| Related Clinical Trial | |||||
| NCT Number | NCT05647122 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1, multicenter, open-label, first-in-human, dose escalation and expansion study of AZD9592 as monotherapy and in combination with anti-cancer agents in patients with advanced solid tumors.
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References