Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0FMCLF
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| ADC Name |
Anbenitamab repodatecan
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| Synonyms |
anbenitamab repodatecan; JSKN-003; JSKN003; KN026-ADC
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| Organization |
Alphamab Oncology (Originator);CSPC Pharmaceutical Group
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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 |
Anbenitamab
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Antibody Info | ||||
| Antigen Name |
Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)
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Antigen Info | ||||
| Payload Name |
DXd
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Payload Info | ||||
| Therapeutic Target |
DNA topoisomerase 1 (TOP1)
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Target Info | ||||
| Linker Name |
DBCO-PEG4-Mc-Gly-Gly-Phe-Gly
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Linker Info | ||||
| Conjugate Type |
Enzymatic Catalysis
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| Combination Type |
repodatecan
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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 |
2 Trials
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| Colorectal cancer |
1 Trials
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| Fallopian tube cancer |
1 Trials
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| Ovarian cancer |
1 Trials
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| Peritoneal cancer |
1 Trials
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| Unspecific solid tumor |
1 Trials
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General Information of The ADMET Data Related to This ADC(2027 Update)
Excretion
| Standard Type | Value | Units | Description | Reference |
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| Elimination Half-Life (t1/2) | 5-6 | day |
Half-life of JSKN003 is approximately 5-6 days for 6.3 mg/kg and higher doses and increases with dose escalation.
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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] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
50%
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| Patients Enrolled |
Eligible patients require HER2-positive (IHC≥1+) advanced solid tumors (ECOG 0-1, life expectancy ≥12 weeks), measurable disease (RECIST 1.1), adequate organ function, and no recent transfusions/G-CSF. Key exclusions include untreated CNS metastases, LVEF<50%, or pregnancy. Contraception is mandated for 180 days post-treatment.
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| Administration Dosage |
.
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| Related Clinical Trial | |||||
| NCT Number | NCT05494918 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I, Multi-center, Open-label, Dose Escalation, First-In-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of JSKN003 in Subjects With Advanced or Metastatic Solid Malignant Tumors | ||||
| Primary Endpoint |
Primary objectives include determining MTD/RP2D, assessing DLTs within 21 days post-first dose, and monitoring safety (TEAEs/TRAEs/SAEs) up to 1 year post-treatment.
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| Other Endpoint |
Secondary endpoints cover PK profiling (Cmax/Tmax/AUC/t½ of JSKN003 up to Day 90), efficacy measures (ORR/TTR/DoR/PFS per RECIST v1.1 over 1 year), and immunogenicity (anti-drug antibodies).
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| Experiment 2 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Objective Response Rate (ORR) |
51.40%
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| Patients Enrolled |
Eligible patients must have advanced/metastatic solid tumors (ECOG 0-1, life expectancy ≥12 weeks), measurable disease (RECIST 1.1), adequate organ function, and provide tumor samples. Fertile subjects require contraception until 180 days post-treatment.
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| Administration Dosage |
JSKN003 should be administered intravenously on the first day of each 3-week cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT05744427 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of JSKN003 in Chinese Subjects With Advanced Solid Tumors | ||||
| Primary Endpoint |
Primary endpoints include DLT assessment (dose escalation phase), MTD/RP2D determination (BOIN design), safety monitoring (TEAEs/SAEs per CTCAE v5.0 over 2 years), and ORR evaluation (RECIST v1.1 in phase 2).
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| Other Endpoint |
Secondary measures comprise efficacy (CBR, PFS, DOR), PK parameters (Cmax/Tmax/AUC/t½ of JSKN003), and immunogenicity (anti-drug antibodies) throughout the 2-year study duration.
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| Experiment 3 Reporting the Activity Date of This ADC | [4] | ||||
| Efficacy Data | Disease control rate (DCR) |
75%
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| Patients Enrolled |
Eligible patients must have HER2-expressing (IHC≥1+ or NSCLC mutations) advanced solid tumors (ECOG 0-1, life expectancy ≥12 weeks), measurable disease (RECIST 1.1), adequate organ function, and no prior topoisomerase I inhibitor ADCs. Key exclusions include active CNS metastases, uncontrolled comorbidities, unresolved treatment toxicities (>CTCAE v5.0 grade 1), or severe hypersensitivity to HER2 therapies/ADC components.
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| Administration Dosage |
As of August 20, 2024, ten patients had been enrolled (n=4 breast cancer, n=2 NSCLC, n=2 biliary tract cancer, n=1 colorectal cancer, and n=1 salivary gland cancer) (table 1). Patients received JSKN033 at doses of 1.1 mg/kg (n=1), 2.3 mg/kg (n=1), 4.5 mg/kg (n=3), 5.6 mg/kg (n=3), and 6.7 mg/kg (n=2). The most common treatment-related adverse event (TRAE) was mild to moderate injection site reactions (Grade 1-2). No Grade 3 or higher TRAEs or serious adverse events were observed, and no TRAEs led to treatment discontinuation.
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| Related Clinical Trial | |||||
| NCT Number | NCT06226766 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of JSKN033 in Patients With Advanced or Metastatic Solid Malignant Tumors | ||||
| Primary Endpoint |
Primary endpoints include safety assessment (TEAEs/TRAEs/SAEs per CTCAE v5.0 over 1 year), RP2D determination, DLT evaluation (first 21 days), and investigator-assessed ORR (RECIST v1.1 criteria within 1 year post-treatment).
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| Other Endpoint |
Secondary endpoints comprise PK analysis (Cmax/Tmax/AUC for JSKN003 components over 1 year), efficacy outcomes (investigator-assessed PFS/DoR/OS per RECIST v1.1 within 1 year), and immunogenicity monitoring.
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| Experiment 4 Reporting the Activity Date of This ADC | [2] | ||||
| Efficacy Data | Disease control rate (DCR) |
90.60%
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| Patients Enrolled |
Eligible patients require HER2-positive (IHC≥1+) advanced solid tumors (ECOG 0-1, life expectancy ≥12 weeks), measurable disease (RECIST 1.1), adequate organ function, and no recent transfusions/G-CSF. Key exclusions include untreated CNS metastases, LVEF<50%, or pregnancy. Contraception is mandated for 180 days post-treatment.
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| Administration Dosage |
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| Related Clinical Trial | |||||
| NCT Number | NCT05494918 | Clinical Status | PHASE1 | ||
| Clinical Description | A Phase I, Multi-center, Open-label, Dose Escalation, First-In-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of JSKN003 in Subjects With Advanced or Metastatic Solid Malignant Tumors | ||||
| Primary Endpoint |
Primary objectives include determining MTD/RP2D, assessing DLTs within 21 days post-first dose, and monitoring safety (TEAEs/TRAEs/SAEs) up to 1 year post-treatment.
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| Other Endpoint |
Secondary endpoints cover PK profiling (Cmax/Tmax/AUC/t½ of JSKN003 up to Day 90), efficacy measures (ORR/TTR/DoR/PFS per RECIST v1.1 over 1 year), and immunogenicity (anti-drug antibodies).
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| Experiment 5 Reporting the Activity Date of This ADC | [3] | ||||
| Efficacy Data | Disease control rate (DCR) |
91.90%
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| Patients Enrolled |
Eligible patients must have advanced/metastatic solid tumors (ECOG 0-1, life expectancy ≥12 weeks), measurable disease (RECIST 1.1), adequate organ function, and provide tumor samples. Fertile subjects require contraception until 180 days post-treatment.
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| Administration Dosage |
JSKN003 should be administered intravenously on the first day of each 3-week cycle.
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| Related Clinical Trial | |||||
| NCT Number | NCT05744427 | Clinical Status | PHASE1|||PHASE2 | ||
| Clinical Description | Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of JSKN003 in Chinese Subjects With Advanced Solid Tumors | ||||
| Primary Endpoint |
Primary endpoints include DLT assessment (dose escalation phase), MTD/RP2D determination (BOIN design), safety monitoring (TEAEs/SAEs per CTCAE v5.0 over 2 years), and ORR evaluation (RECIST v1.1 in phase 2).
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| Other Endpoint |
Secondary measures comprise efficacy (CBR, PFS, DOR), PK parameters (Cmax/Tmax/AUC/t½ of JSKN003), and immunogenicity (anti-drug antibodies) throughout the 2-year study duration.
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| Experiment 6 Reporting the Activity Date of This ADC | [5] | ||||
| Patients Enrolled |
Eligible patients must have HER2-low (IHC 1+/2+ ISH-) unresectable/metastatic breast cancer (≥18 years, ECOG 0-1) with ≥1 measurable lesion, 1-2 prior chemotherapy lines, adequate organ function, and no prior HER2-targeted ADC therapy or topoisomerase I inhibitor ADCs.
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| Administration Dosage |
.
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| Related Clinical Trial | |||||
| NCT Number | NCT06079983 | Clinical Status | PHASE3 | ||
| Clinical Description | A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects | ||||
| Primary Endpoint |
The primary endpoint is PFS (BICR-assessed per RECIST v1.1) with secondary endpoints including OS, ORR, and DOR (both BICR/investigator-assessed) evaluated at 16/26 months (extended to 60 months for OS).
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| Other Endpoint |
Efficacy assessments focus on time-to-event outcomes (PFS/OS/DOR) and tumor response rates (ORR) using RECIST v1.1 criteria through multiple evaluation timepoints up to 60 months.
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| Experiment 7 Reporting the Activity Date of This ADC | [6] | ||||
| Patients Enrolled |
Key eligibility requires HER2-positive (IHC 3+ or 2+/ISH+) unresectable/metastatic breast cancer patients (≥18y, ECOG 0-1) with prior trastuzumab/taxane exposure, measurable lesions (RECIST 1.1), adequate organ function, and ≥3-month life expectancy.
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| Administration Dosage |
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| Related Clinical Trial | |||||
| NCT Number | NCT06846437 | Clinical Status | PHASE3 | ||
| Clinical Description | A Randomized, Controlled, Open-Label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of JSKN003 Versus Trastuzumab Emtansine (T-DM1) for HER2-Positive, Advanced Breast Cancer Subjects | ||||
| Primary Endpoint |
The primary endpoint is PFS assessed by BIRC per RECIST v1.1 with a 4-year timeframe, alongside comprehensive safety monitoring including TEAEs and SAEs from consent through follow-up.
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| Other Endpoint |
Secondary outcomes include investigator-evaluated PFS, OS, ORR, DCR, DoR over 4 years, plus PK (Cmax/AUC) and immunogenicity (ADA) profiles of JSKN003 across treatment cycles.
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References