Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0VJROY
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| ADC Name |
Sigvotatug vedotin
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| Synonyms |
sigvotatug vedotin; SGN-B6A; PF-08046047
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| Organization |
Seagen (Top20 MNC) (Originator)
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| Drug Status |
Phase 3
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| Drug-to-Antibody Ratio |
4
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| Structure |
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| Antibody Name |
Sigvotatug
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Antibody Info | ||||
| Antigen Name |
Integrin beta-6 (ITGB6)
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Antigen Info | ||||
| Payload Name |
MMAE
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Payload Info | ||||
| Therapeutic Target |
Microtubule (MT)
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Target Info | ||||
| Linker Name |
Mc-Val-Cit-PABC
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Linker Info | ||||
| Conjugate Type |
Random Cysteines
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| Combination Type |
vedotin
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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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| Breast cancer |
1 Trials
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| Cervical cancer |
1 Trials
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| Gastric cancer |
2 Trials
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| Gastroesophageal junction adenocarcinoma |
2 Trials
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| Head and neck cancer |
2 Trials
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| Lung cancer |
2 Trials
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1 Trials
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| Oesophageal cancer |
2 Trials
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| Ovarian cancer |
1 Trials
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| Pancreatic cancer |
1 Trials
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| Urothelial cancer |
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 |
|---|---|---|---|---|
| Maximum Observed Concentration (Cmax) | 115000 | ng/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 199000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg, AUC0-7d.
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[1] |
| Maximum Observed Concentration (Cmax) | 162000 | ng/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 282000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg, AUC0-7d.
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[1] |
| Maximum Observed Concentration (Cmax) | 299000 | ng/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg.
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| Area Under the Concentration-Time Curve (AUC) | 426000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg, AUC0-7d.
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[1] |
| Maximum Observed Concentration (Cmax) | 295000 | ng/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 501000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg, AUC0-7d.
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[1] |
Distribution
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 199000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg, AUC0-7d.
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| Volume of Distribution (Vd) | 40.4 | mL/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 282000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg, AUC0-7d.
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[1] |
| Volume of Distribution (Vd) | 42 | mL/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 426000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg, AUC0-7d.
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[1] |
| Volume of Distribution (Vd) | 35.9 | mL/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 501000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg, AUC0-7d.
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[1] |
| Volume of Distribution (Vd) | 37.6 | mL/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg.
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[1] |
Metabolism
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 199000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg, AUC0-7d.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 282000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg, AUC0-7d.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 426000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg, AUC0-7d.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 501000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg, AUC0-7d.
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[1] |
Excretion
| Standard Type | Value | Units | Description | Reference |
|---|---|---|---|---|
| Area Under the Concentration-Time Curve (AUC) | 199000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg, AUC0-7d.
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| Elimination Half-Life (t1/2) | 2.31 | day |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg.
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| Clearance (CL) | 13.6 | mL/day/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 3 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 282000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg, AUC0-7d.
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[1] |
| Elimination Half-Life (t1/2) | 2.58 | day |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg.
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[1] |
| Clearance (CL) | 12.4 | mL/day/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 4 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 426000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg, AUC0-7d.
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[1] |
| Elimination Half-Life (t1/2) | 2.98 | day |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg.
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[1] |
| Clearance (CL) | 9.86 | mL/day/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 5 mg/kg.
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[1] |
| Area Under the Concentration-Time Curve (AUC) | 501000 | ng*day/mL |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg, AUC0-7d.
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[1] |
| Elimination Half-Life (t1/2) | 3.53 | day |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg.
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[1] |
| Clearance (CL) | 9.77 | mL/day/kg |
Pharmacokinetic parameters of SGN-B6A in cynomolgus monkeys, 6 mg/kg.
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[1] |
General Information of The Activity Data Related to This ADC
Identified from the Human Clinical Data
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] | ||||
| Patients Enrolled |
Patients with metastatic or unresectable solid tumors.
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| Administration Dosage |
30 patients in Q1W (0.80, 1.00, and 1.20 mg/kg); 18 patients in 2Q3W (1.20 or 1.25 mg/kg).
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| Related Clinical Trial | |||||
| NCT Number | NCT04389632 | Clinical Status | Phase 1/2 | ||
| Clinical Description | A phase 1 study of SGN-B6A in advanced solid tumors. | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
19.5
32.5 % |
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| Patients Enrolled |
Eligible participants must have metastatic/unresectable solid tumors (e.g., NSCLC, HNSCC, HER2-negative breast cancer) and meet cohort-specific requirements: Part A (refractory to standard therapies), Part B (prior platinum/PD-1 therapy), Part C/D (treatment-naïve for advanced disease where applicable). Key exclusions: active CNS metastases (exceptions for stable, treated cases), prior MMAE/integrin beta-6 therapy, Grade ≥2 neuropathy (Grade ≥1 for cisplatin/carboplatin cohorts), unresolved ILD/pneumonitis, or DLCO <50%.
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| Administration Dosage |
Eligible pts had no therapeutic options (Part A) or had received platinum-based and anti-PD- (L)1 therapy unless contraindicated (Part B) and were dosed with the SV expansion regimens on D1 and D8 in a 21-day cycle (2Q3W; 1.2/1.25 mg/kg total body weight [TBW]) or D1 and D15 in a 28-day cycle (2Q4W; 1.5 mg/kg TBW, 1.8 mg/kg adjusted ideal body weight [AiBW]).
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| Related Clinical Trial | |||||
| NCT Number | NCT04389632 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase 1 Study of SGN-B6A in Advanced Solid Tumors | ||||
| Primary Endpoint |
Safety endpoints include the number of participants experiencing adverse events (AEs), laboratory abnormalities, and dose-limiting toxicities (DLTs), assessed up to 3 years, with AE monitoring extended to 90 days post-pembrolizumab for relevant cohorts.
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| Other Endpoint |
Efficacy measures consist of confirmed objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS), all per RECIST v1.1. Pharmacokinetic (PK) parameters-AUC, Cmax, Tmax, Ctrough, and t1/2-as well as antidrug antibodies (ADAs), will be evaluated up to 3 years post-treatment.
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| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Patients Enrolled |
Eligible patients must have specific advanced solid tumors (NSCLC, HNSCC, ESCC, GAC/EAC/GEJ) refractory to standard therapies, adequate organ function, and ECOG 0-1. Key exclusions include recent malignancies, pulmonary complications ≥Grade 3, active CNS metastases, prior MMAE treatment, and recent anticancer therapies/herbals with defined washout periods.
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| Administration Dosage |
sigvotatug vedotin monotherapy 1.8 mg/kg adjusted ideal body weight intravenous administration on Days 1 and 15 of a 28-day cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT06549816 | Clinical Status | PHASE1 | ||
| Clinical Description | An Open-label, Phase 1 Study to Investigate the Safety and Pharmacokinetics of SGN-B6A in Chinese Subjects With Advanced Solid Tumors | ||||
| Primary Endpoint |
Primary endpoints include AE assessment over 3 years, lab abnormalities tracking within 30-37 days post-treatment, and DLT monitoring during the initial 28-day period following sigvotatug vedotin administration.
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| Other Endpoint |
Pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2, Ctrough) for both ac-MMAE and MMAE will be evaluated following single and multiple doses of SGN-B6A across two treatment cycles (28 days each), along with antidrug antibody detection up to 37 days post-treatment.
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| Experiment 4 Reporting the Activity Date of This ADC | [5] | ||||
| Patients Enrolled |
Eligible patients must have unresectable/metastatic non-squamous NSCLC (Stage IIIB-IV per AJCC v8), measurable disease (RECIST v1.1), and progression after platinum/PD- (L)1 therapy (or AGA-targeted therapy if applicable). Key exclusions include life expectancy <3 months, prior taxanes/MMAE exposure in metastatic setting, unresolved Grade ≥2 neuropathy, uncontrolled ILD (steroid-dependent or DLCO <50%), active CNS metastases (unless stable for ≥4 weeks post-treatment with steroids ≤10mg/day), and recent anticancer therapy (<21 days before C1D1).
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| Administration Dosage |
Given into the vein (IV; intravenously) on Day 1 and 15 of a 28-day cycle
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| Related Clinical Trial | |||||
| NCT Number | NCT06012435 | Clinical Status | PHASE3 | ||
| Clinical Description | A Randomized, Phase 3, Open-label Study to Evaluate Sigvotatug Vedotin Compared With Docetaxel in Adult Participants With Previously Treated Non-small Cell Lung Cancer (Be6A Lung-01) | ||||
| Primary Endpoint |
The primary efficacy endpoints include OS (time from randomization to death) and PFS per RECIST v1.1 (time to disease progression or death) comparing sigvotatug vedotin versus docetaxel in both the overall population and IB6-high subgroup over 5 years.
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| Other Endpoint |
Secondary endpoints include ORR per RECIST v1.1 (confirmed CR/PR rates by BICR and investigator assessment), DOR (time from response to progression/death), AEs within 30 days post-treatment, and quality-of-life metrics (EORTC QLQ-C30 and QLQ-LC13) assessing global health status, physical/role functioning, and symptom scales (dyspnea, cough, chest pain), along with TTD for key PROs over 5 years of follow-up.
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References