ADC ID	DRG0SIMLV
ADC Name	ESG401
Synonyms	ESG401; ESG-401; STI-3258; OQY-3258    Click to Show/Hide
Organization	Levena Biopharma (Originator);Shanghai Escugen Biotechnology (Escugen) (Originator);Oqory
Drug Status	Phase 3
Drug-to-Antibody Ratio	8
				2D MOL
Antibody Name	Anti-TROP2 IgG1 mAb					Antibody Info
Antigen Name	Tumor-associated calcium signal transducer 2 (TACSTD2); Programmed cell death 1 ligand 1 (PD-L1)					Antigen Info
Payload Name	SN-38					Payload Info
Therapeutic Target	DNA topoisomerase 1 (TOP1)					Target Info
Linker Name	A proprietary stable-cleavable linker					Linker Info
Conjugate Type	Undisclosed

Standard Type	Value	Units	Description	Reference
Time to Maximum Concentration (Tmax)	0.0833-0.5	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg.	[1]
Time to Maximum Concentration (Tmax)	0.0833	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg.	[1]
Time to Maximum Concentration (Tmax)	0.0833	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg.	[1]
Maximum Observed Concentration (Cmax)	24±3.09	ug/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg.	[1]
Maximum Observed Concentration (Cmax)	132±7.53	ug/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg.	[1]
Maximum Observed Concentration (Cmax)	763±177	ug/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	294±108	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1590±345	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	12600±3700	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg, AUC0-t.	[1]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	294±108	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1590±345	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	12600±3700	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg, AUC0-t.	[1]
Volume of Distribution (Vd)	107±46.9	mL/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg.	[1]
Volume of Distribution (Vd)	175±49.9	mL/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg.	[1]
Volume of Distribution (Vd)	135±41.3	mL/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg.	[1]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	294±108	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1590±345	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	12600±3700	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg, AUC0-t.	[1]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	20.2±7.24	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg.	[1]
Elimination Half-Life (t1/2)	37.8±4.89	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg.	[1]
Elimination Half-Life (t1/2)	46.3±12.6	h	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	294±108	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1590±345	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	12600±3700	ug*h/mL	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg, AUC0-t.	[1]
Clearance (CL)	3.77±1.42	mL/h/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 1mg/kg.	[1]
Clearance (CL)	3.2±0.831	mL/h/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 5mg/kg.	[1]
Clearance (CL)	2.12±0.671	mL/h/kg	Pharmacokinetic parameters of ESG401 after single intravenous dose in cynomolgus macaques (relevant species). Related to the STAR Methods, IV 25mg/kg.	[1]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT04892342	PHASE1|||PHASE2	An Open-Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of ESG401 in Subjects With Locally Advanced/Metastatic Solid Tumors    Click to Show/Hide
Disease control rate (DCR)	NCT04892342	PHASE1|||PHASE2	An Open-Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of ESG401 in Subjects With Locally Advanced/Metastatic Solid Tumors    Click to Show/Hide
Undisclosed	NCT06383767	PHASE3	A Open-label, Randomized, Multicenter Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Had Failed at Least One Line of Chemotherapy    Click to Show/Hide
Undisclosed	NCT06732323	PHASE3	A Randomized, Open-label, Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy as First-line Treatment in Patients With Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer    Click to Show/Hide
Undisclosed	NCT06145308	PHASE2	Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center of China
Objective Response Rate (ORR)	NCT04892342	Phase 1/2	An open-label, multiple dose, dose escalation and cohort expansion phase 1/2 study to investigate the safety, tolerability, pharmacokinetics and antitumor activities of ESG401 in Subjects with locally advanced/metastatic solid tumors.    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Objective Response Rate (ORR)	34.20%
Patients Enrolled	Eligibility requires confirmed advanced/metastatic solid tumors, ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function, excluding recent cancer therapy, unresolved toxicities (>Grade 1), major surgery, active infections, uncontrolled comorbidities (CNS, cardiovascular, hepatic, GI), HIV/hepatitis B/C, drug hypersensitivity, or pregnancy risk. Exclusions also cover conditions jeopardizing protocol compliance.    Click to Show/Hide
Administration Dosage	The initial dose-escalation study design included 6 dose levels ranging from 2 mg/kg to 20 mg/kg administered every 3 weeks (Q3 weeks), with a total of 17 subjects enrolled.
Related Clinical Trial
NCT Number	NCT04892342	Clinical Status	PHASE1|||PHASE2
Clinical Description	An Open-Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of ESG401 in Subjects With Locally Advanced/Metastatic Solid Tumors
Primary Endpoint	The study evaluates treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded by CTCAE v5.0, occurring from first dose until 30 days post-treatment. Key efficacy measures include Objective Response Rate (ORR) by Independent Central Review (ICR) using RECIST 1.1 criteria, with CR/PR definitions for tumor assessment, analyzed in the TNBC Target Population during phase 2 over 49 months.    Click to Show/Hide
Other Endpoint	Pharmacokinetic parameters (Cmax, AUC0-inf) and immunogenicity (ADA incidence) are assessed over 49 months. Additional efficacy endpoints include ORR and Progression-Free Survival (PFS) by local assessment, along with Overall Survival (OS), measured from the first dose in both phase 1 and phase 2.
Experiment 2 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Disease control rate (DCR)	65.80%
Patients Enrolled	Eligibility requires confirmed advanced/metastatic solid tumors, ECOG 0-1, life expectancy ≥12 weeks, and adequate organ function, excluding recent cancer therapy, unresolved toxicities (>Grade 1), major surgery, active infections, uncontrolled comorbidities (CNS, cardiovascular, hepatic, GI), HIV/hepatitis B/C, drug hypersensitivity, or pregnancy risk. Exclusions also cover conditions jeopardizing protocol compliance.    Click to Show/Hide
Administration Dosage	The initial dose-escalation study design included 6 dose levels ranging from 2 mg/kg to 20 mg/kg administered every 3 weeks (Q3 weeks), with a total of 17 subjects enrolled.
Related Clinical Trial
NCT Number	NCT04892342	Clinical Status	PHASE1|||PHASE2
Clinical Description	An Open-Label, Multiple Dose, Dose Escalation and Cohort Expansion Phase I/II Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of ESG401 in Subjects With Locally Advanced/Metastatic Solid Tumors
Primary Endpoint	The study evaluates treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded by CTCAE v5.0, occurring from first dose until 30 days post-treatment. Key efficacy measures include Objective Response Rate (ORR) by Independent Central Review (ICR) using RECIST 1.1 criteria, with CR/PR definitions for tumor assessment, analyzed in the TNBC Target Population during phase 2 over 49 months.    Click to Show/Hide
Other Endpoint	Pharmacokinetic parameters (Cmax, AUC0-inf) and immunogenicity (ADA incidence) are assessed over 49 months. Additional efficacy endpoints include ORR and Progression-Free Survival (PFS) by local assessment, along with Overall Survival (OS), measured from the first dose in both phase 1 and phase 2.
Experiment 3 Reporting the Activity Date of This ADC					[2]
Patients Enrolled	The study emphasized safety (monitoring AEs/SAEs), efficacy (PFS, OS, ORR, CBR, DoR), and pharmacokinetics (clearance, volume of distribution) over 24 months, with stringent enrollment criteria targeting refractory HR+/HER2- breast cancer patients while excluding those with significant prior treatments, comorbidities, or pregnancy/lactation.
Administration Dosage	IV infusion on day 1, 8 and15 of each 28 day cycle
Related Clinical Trial
NCT Number	NCT06383767	Clinical Status	PHASE3
Clinical Description	A Open-label, Randomized, Multicenter Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Had Failed at Least One Line of Chemotherapy
Primary Endpoint	The primary endpoint was progression-free survival (PFS) assessed by IRC and investigators per RECIST 1.1, measuring time from randomization to PD or death over 24 months. Key secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DoR), all evaluated over 24 months using RECIST 1.1 criteria. Quality of life was assessed via NCC-BC-A scale, while safety covered AEs, SAEs (CTCAE 5.0), pharmacokinetic parameters (clearance, volume of distribution), and ADA incidence.    Click to Show/Hide
Other Endpoint	Eligible patients were adults (≥18 years) with HR+/HER2- breast cancer failing ≥1 line of chemotherapy, measurable lesions per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions included recent anti-cancer therapies (within 4 weeks), unresolved toxicities (>Grade 1), major surgery within 4 weeks, prior topoisomerase I/TROP2 inhibitors, untreated CNS metastases, active infections, uncontrolled comorbidities (cardiovascular, GI, HIV, hepatitis B/C), or hypersensitivity to irinotecan/excipients.    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Key inclusion criteria include adults ≥18 years with histologically confirmed TNBC (metastatic or relapsed), no prior systemic therapy for advanced disease, PD-L1-negative or PD-L1-positive post-relapse, measurable lesions, ECOG 0-1, and adequate organ function. Exclusion criteria cover recent investigational drugs, prior topoisomerase I/TROP2 therapy, severe comorbidities (CNS metastases, cardiovascular disease, uncontrolled infections, gastrointestinal disorders), drug hypersensitivity, and pregnancy/lactation.    Click to Show/Hide
Administration Dosage	IV infusion on day 1, 8 and15 of each 28 day cycle
Related Clinical Trial
NCT Number	NCT06732323	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-label, Phase III Study of ESG401 Versus Investigator's Choice Chemotherapy as First-line Treatment in Patients With Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer
Primary Endpoint	The primary endpoints include Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) and Overall Survival (OS). PFS is defined as the time from randomization to disease progression per RECIST 1.1 or death, while OS measures time from randomization to any-cause death, with follow-up periods of approximately 28 and 41 months, respectively.    Click to Show/Hide
Other Endpoint	Secondary endpoints encompass investigator-assessed PFS, Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DoR), and Time to Response (TTR) evaluated by both BICR and investigator. Additional assessments include Quality of Life via NCC-BC-A scale, safety analysis for AEs/SAEs, pharmacokinetic parameters (clearance, volume of distribution), and immunogenicity measurement (anti-drug antibodies), with evaluations spanning approximately 28 months.    Click to Show/Hide
Experiment 5 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Eligible patients require histopathologically confirmed salivary gland carcinoma with specific biomarker testing, good ECOG status (0-1), measurable lesions per RECIST 1.1, and adequate organ function. Exclusions include treatment allergies, recent major surgery/vaccination, active infections, major cardiovascular diseases, uncontrolled comorbidities, or pregnancy/breastfeeding.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT06145308	Clinical Status	PHASE2
Clinical Description	Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center of China
Primary Endpoint	The study evaluates ORR in patients with advanced salivary gland cancer at the end of Cycle 3 (14 days per cycle) for neoadjuvant/translational therapy and salvage therapy in cases of rapid progression where surgery is not tolerated or refused.
Other Endpoint	Key secondary endpoints include MPR rate, R0 resection rate, facial nerve protection rate post-surgery, 3-year DFS for surgical patients, 2-year PFS for rescue therapy recipients, and 5-year OS for all participants.
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Objective Response Rate (ORR)	36.40%
Patients Enrolled	Patients (pts) aged 18 years with locally advanced/metastatic solid tumors refractory to/relapsed.
Administration Dosage	Treated with 1 dose of ESG401 during escalation at doses of 2-20 mg/kg once Q3W (Regimen A), or 12-16 mg/kg D1,8,15 in a 4-week cycle (Regimen B).
Related Clinical Trial
NCT Number	NCT04892342	Clinical Status	Phase 1/2
Clinical Description	An open-label, multiple dose, dose escalation and cohort expansion phase 1/2 study to investigate the safety, tolerability, pharmacokinetics and antitumor activities of ESG401 in Subjects with locally advanced/metastatic solid tumors.

Ref 1	Phase 1a study of ESG401, a Trop2 antibody-drug conjugate, in patients with locally advanced/metastatic solid tumors
Ref 2	A Phase III Study of ESG401 for Locally Advanced or Metastatic HR+/HER2- Breast Cancer
Ref 3	A Phase III Study of ESG401 for Unresectable Recurrent or Metastatic Triple-Negative Breast Cancer
Ref 4	Precision Treatment of Recurrent/Metastatic Salivary Gland Carcinoma Guided by Molecular Typing
Ref 5	Preliminary results from a first-in-human study of ESG401, a trophoblast cell-surface antigen 2 (TROP2) antibody drug conjugate (ADC), in patients with locally advanced/metastatic solid tumors. J Clin Oncol. 2023 41:16_suppl, 1100-1100.