Linker Information
General Information of This Linker
| Linker ID |
LIN0KQAXA
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| Linker Name |
Mc-PEG8-acid-labile linker
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| Linker Type |
Flexible reactive (thiol) linker
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| Antibody-Linker Relation |
Uncleavable
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| Structure |
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| Formula |
C26H45N3O11
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| Isosmiles |
NCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCC1C(=O)C=CC1=O
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| InChI |
InChI=1S/C26H45N3O11/c27-21-29-26(33)5-7-34-9-11-36-13-15-38-17-19-40-20-18-39-16-14-37-12-10-35-8-6-28-25(32)4-1-22-23(30)2-3-24(22)31/h2-3,22H,1,4-21,27H2,(H,28,32)(H,29,33)
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| InChIKey |
VGFGTEUWYBXHHK-UHFFFAOYSA-N
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| Pharmaceutical Properties |
Molecule Weight
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575.656
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Polar area
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182.97
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Complexity
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40
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xlogp Value
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-1.2543
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Heavy Count
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40
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Rot Bonds
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28
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Hbond acc
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12
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Hbond Donor
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3
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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
ABBV-011 [Phase 1 (discontinued)]
Identified from the Human Clinical Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
25%
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| Patients Enrolled |
Eligible participants have relapsed/refractory SCLC (1-3 prior lines), measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions: cirrhosis, cardiac disease (>6 months prior), active infections, autoimmune/neurologic conditions, or hypersensitivity to study drugs. SEZ6+ tumor tissue is required for Parts B/C. Additional exclusions for Part C include neuropathy ≥G2, IBD, or prior anti-PD-1/PD-L1 with unresolved irAEs.
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| Administration Dosage |
ABBV-011 was administered intravenously at doses from 0.3 to 2.0 mg/kg once every 3 weeks. Dose expansion was conducted in SEZ6-selected patients.
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| Related Clinical Trial | |||||
| NCT Number | NCT03639194 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase I Study of ABBV-011 as a Single-Agent and in Combination With Budigalimab (ABBV-181) in Subjects With Relapsed or Refractory Small Cell Lung Cancer
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| Primary Endpoint |
The study evaluates AEs, SAEs, DLTs, and determines MTD/RP2D for ABBV-011 alone and in combination with budigalimab over ~5 years, alongside monitoring vital signs, lab abnormalities, and ECG changes.
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| Other Endpoint |
PK parameters (Cmax, AUC, Tmax, T1/2, etc.) and immunogenicity (ADA) for ABBV-011 are assessed. Efficacy endpoints include ORR, CBR, DOR, DOCB, PFS, and OS per RECIST v1.1 over ~5 years.
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| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Clinical benefit rate (CBR) |
64%
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| Patients Enrolled |
Eligible participants have relapsed/refractory SCLC (1-3 prior lines), measurable disease (RECIST v1.1), ECOG 0-1, and adequate organ function. Key exclusions: cirrhosis, cardiac disease (>6 months prior), active infections, autoimmune/neurologic conditions, or hypersensitivity to study drugs. SEZ6+ tumor tissue is required for Parts B/C. Additional exclusions for Part C include neuropathy ≥G2, IBD, or prior anti-PD-1/PD-L1 with unresolved irAEs.
Click to Show/Hide
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| Administration Dosage |
ABBV-011 was administered intravenously at doses from 0.3 to 2.0 mg/kg once every 3 weeks. Dose expansion was conducted in SEZ6-selected patients.
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| Related Clinical Trial | |||||
| NCT Number | NCT03639194 | Clinical Status | PHASE1 | ||
| Clinical Description |
A Phase I Study of ABBV-011 as a Single-Agent and in Combination With Budigalimab (ABBV-181) in Subjects With Relapsed or Refractory Small Cell Lung Cancer
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| Primary Endpoint |
The study evaluates AEs, SAEs, DLTs, and determines MTD/RP2D for ABBV-011 alone and in combination with budigalimab over ~5 years, alongside monitoring vital signs, lab abnormalities, and ECG changes.
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| Other Endpoint |
PK parameters (Cmax, AUC, Tmax, T1/2, etc.) and immunogenicity (ADA) for ABBV-011 are assessed. Efficacy endpoints include ORR, CBR, DOR, DOCB, PFS, and OS per RECIST v1.1 over ~5 years.
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| Experiment 3 Reporting the Activity Date of This ADC | [2] | ||||
| Related Clinical Trial | |||||
| NCT Number | NCT03639194 | Clinical Status | Phase 1 | ||
| Clinical Description |
A phase 1 study of ABBV-011 as a single-agent and in combination with budigalimab (ABBV-181) in subjects with relapsed or refractory small cell lung cancer.
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Discovered Using Patient-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 15.30% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 LD(NAC-LD19.10)=0.24 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU64) | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 35.60% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU149) | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 42.85% | Negative SEZ6 expression (SEZ6-) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU505) | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 45.90% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=8mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU505) | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 71.70% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=1 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU149) | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 87% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
NAC-LD19.10 ADC=8mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU505) | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 89.80% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=1 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU95) | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 89.80% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU149) | ||||
| Experiment 9 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 92% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=0.5 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU64) | ||||
| Experiment 10 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 93.50% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=2 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU149) | ||||
| Experiment 11 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 94.78% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU95) | ||||
| Experiment 12 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU64) | ||||
| Experiment 13 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 96.80% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=2 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU95) | ||||
| Experiment 14 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 97% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=4 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU95) | ||||
| Experiment 15 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=1 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU64) | ||||
| Experiment 16 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.40% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=2 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU64) | ||||
| Experiment 17 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 98.70% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 ADC=4 mg/kg.
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| In Vivo Model | SCLC PDX model (PDX: LU149) | ||||
| Experiment 18 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.60% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU95) | ||||
| Experiment 19 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 99.80% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU95) | ||||
| Experiment 20 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU149) | ||||
| Experiment 21 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU64) | ||||
| Experiment 22 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) | ≈ 100% | Positive SEZ6 expression (SEZ6+++/++) | ||
| Method Description |
ABBV-011 induces efficient tumor cell killing in cell line-derived models of LU64 and LU149 cells with SC17 expression with high expression.
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| In Vivo Model | Small cell lung cancer PDX model (PDX: LU64) | ||||
References