ADC ID	DRG0TPQUN
ADC Name	Bulumtatug fuvedotin
Synonyms	bulumtatug fuvedotin; 9MW2821    Click to Show/Hide
Organization	Mabwell Bioscience (Originator);Shanghai Institute of Materia Medica (SIMM, CAS) (No Rights)
Drug Status	Phase 3
Drug-to-Antibody Ratio	4
Structure
				2D MOL
Antibody Name	Bulumtatug					Antibody Info
Antigen Name	Nectin-4 (NECTIN4)					Antigen Info
Payload Name	MMAE					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	IDM-Val-Cit-PBCA					Linker Info
Conjugate Type	Reactive Cysteines
Combination Type	fuvedotin

Bystander Killing Effect	Description	Reference
yes	The bystander cytotoxicity effect is typically attributed to ADC that release cell-permeable payloads and has been demonstrated for MMAE ADC in several studies. The bystander effect may have a positive impact in decreasing tumor stroma and tumor cells with no or less target expression, thereby enhancing the antitumor effectiveness of ADC. To investigate the bystander killing effect of 9MW2821 and EV, we conducted a coculture cell killing assay. PC-3 cells (3 × 104) were mixed with PC-3/nectin-4 cells at ratios from 0 to 6 × 104. In the absence of PC-3/nectin-4 cells, neither 9MW2821 nor EV showed significant growth inhibition of the PC-3 cells. As the number of PC-3/nectin-4 cells was increased, the cell growth inhibition of PC-3 increased. The 9MW2821 and EV conjugates showed similar bystander killing toward the PC-3 cell in the presence of varying numbers of PC-3/nectin-4 cells.    Click to Show/Hide	[1]

Dissocation Constant (Kd)	Binding Target	Description	Reference
6.97 ng/mL	recombinant human nectin-4	The 9MW2821 conjugate had strong and specific binding to recombinant human nectin-4, with EC50 6.97 ng/mL, and it did not bind to nectin-1, nectin-2, or nectin-3.	[1]

Incubation Time	14days	Release	54.5%	Reference	[1]
Incubation Medium	cynomolgus monkey serum
Description	To measure the stability of 9MW2821 and EV in serum in vitro, we used LC/MS-MS and ELISA to measure the concentrations of free MMAE, total antibodies, and ADC during the course of 14 days in cynomolgus monkey serum. The release rate of free MMAE was relatively low and similar for the two ADC as measured by LC/MS-MS (Fig. 4A). However, as measured in an ELISA test, EV degraded more rapidly than 9MW2821. We found that 45.5% of 9MW2821 and 77.7% of EV was degraded in the serum after 14 days.    Click to Show/Hide
Incubation Time	10days	Release	16%	Reference	[1]
Incubation Medium	monkey serum
Description	We studied the stability of 9MW2821 in PMS and PHS at 37°C for up to 10 d. The concentrations of total antibodies, conjugated antibodies, conjugated MMAE, and free MMAE were qualified at different times. After storage for 10 d, the concentration of total antibodies decreased to 75.0 %±4.0 % and 64.6 %±1.6 % of the initial amount in the monkey and human serum, respectively, while the concentration of conjugated antibodies decreased to 84.2 %±3.9 % and 76.7 %±6.3 % of the initial amount in monkey and human serum, respectively.    Click to Show/Hide
Incubation Time	10days	Release	23%	Reference	[1]
Incubation Medium	human serum
Description	We studied the stability of 9MW2821 in PMS and PHS at 37°C for up to 10 d. The concentrations of total antibodies, conjugated antibodies, conjugated MMAE, and free MMAE were qualified at different times. After storage for 10 d, the concentration of total antibodies decreased to 75.0 %±4.0 % and 64.6 %±1.6 % of the initial amount in the monkey and human serum, respectively, while the concentration of conjugated antibodies decreased to 84.2 %±3.9 % and 76.7 %±6.3 % of the initial amount in monkey and human serum, respectively.    Click to Show/Hide

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	24.7	ug/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Maximum Observed Concentration (Cmax)	19.2	ug/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Area Under the Concentration-Time Curve (AUC)	228	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	243	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Maximum Observed Concentration (Cmax)	84	ug/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Maximum Observed Concentration (Cmax)	60.2	ug/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Area Under the Concentration-Time Curve (AUC)	1050	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	897	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Maximum Observed Concentration (Cmax)	154	ug/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Maximum Observed Concentration (Cmax)	102	ug/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Area Under the Concentration-Time Curve (AUC)	2230	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2160	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Time to Maximum Concentration (Tmax)	0.04	d	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice.	[1]
Area Under the Concentration-Time Curve (AUC)	84.2	day*ug/mL	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice, AUC0-t.	[1]
Time to Maximum Concentration (Tmax)	0.08	h	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Maximum Observed Concentration (Cmax)	23.45±2.51	ug/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	324.71±87.58	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	327.41±88.48	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Time to Maximum Concentration (Tmax)	0.08	h	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Maximum Observed Concentration (Cmax)	76.13±6.92	ug/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	1397.73±148.61	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	1406.7±151.2	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Time to Maximum Concentration (Tmax)	0.08	h	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Maximum Observed Concentration (Cmax)	154.1±21.7	ug/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	3044.21±186.54	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	3059.13±185.44	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	228	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	243	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1050	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	897	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2230	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2160	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	84.2	day*ug/mL	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	324.71±87.58	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	327.41±88.48	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	1397.73±148.61	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	1406.7±151.2	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	3044.21±186.54	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	3059.13±185.44	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	228	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	243	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	1050	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	897	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2230	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2160	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	84.2	day*ug/mL	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	324.71±87.58	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	327.41±88.48	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	1397.73±148.61	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	1406.7±151.2	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	3044.21±186.54	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	3059.13±185.44	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	228	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	243	ug*h/mL	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Elimination Half-Life (t1/2)	15	h	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Elimination Half-Life (t1/2)	12.6	h	1 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Area Under the Concentration-Time Curve (AUC)	1050	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	897	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Elimination Half-Life (t1/2)	23	h	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Elimination Half-Life (t1/2)	16.2	h	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Area Under the Concentration-Time Curve (AUC)	2230	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1, AUC0-t.	[1]
Area Under the Concentration-Time Curve (AUC)	2160	ug*h/mL	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22, AUC0-t.	[1]
Elimination Half-Life (t1/2)	22.6	h	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 1.	[1]
Elimination Half-Life (t1/2)	21	h	3 Mg/kg 9MW2821 in cynomolgus monkeys, Day 22.	[1]
Elimination Half-Life (t1/2)	2.1	d	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice.	[1]
Area Under the Concentration-Time Curve (AUC)	84.2	day*ug/mL	Pharmacokinetics studies in 9MW2821 in tumor-bearing mice, AUC0-t.	[1]
Elimination Half-Life (t1/2)	18.7±7.27	h	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	324.71±87.58	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	327.41±88.48	ug*h/mL	Pharmacokinetic parameters of 1 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Elimination Half-Life (t1/2)	26±5.21	h	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	1397.73±148.61	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	1406.7±151.2	ug*h/mL	Pharmacokinetic parameters of 3 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]
Elimination Half-Life (t1/2)	24.03±1.5	h	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey.	[2]
Area Under the Concentration-Time Curve (AUC)	3044.21±186.54	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCtau.	[2]
Area Under the Concentration-Time Curve (AUC)	3059.13±185.44	ug*h/mL	Pharmacokinetic parameters of 6 mg/kg 9MW2821 in cynomolgus monkey, AUCinf.	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT05216965	PHASE1|||PHASE2	Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
Disease control rate (DCR)	NCT05216965	PHASE1|||PHASE2	Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
Undisclosed	NCT06492005	PHASE2	A Phase II Clinical Study of Efficacy and Safety of 9MW2821Monotherapy or Combined With PD-1 Inhibitor in Locally Advanced or Metastatic Triple-Negative Breast Cancer
Undisclosed	NCT06692166	PHASE3	A Randomized, Open-label, Phase 3 Study to Evaluate 9MW2821 vs Treatment of Physician's Choice in Subjects With Recurrent or Metastatic Cervical Cancer Who Progressed on or After Platinum-based Chemotherapy    Click to Show/Hide
Undisclosed	NCT05773937	PHASE1	A Phase I Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Advanced Malignant Solid Tumors
Undisclosed	NCT06079112	PHASE1|||PHASE2	A Phase Ib/II, Open-label, Single Arm, Multicenter Clinical Study to Evaluate the Safety and Efficacy of 9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer    Click to Show/Hide
Undisclosed	NCT06196736	PHASE3	An Open-label, Randomized Phase 3 Study to Evaluate 9MW2821 vs Investigator's Choice of Chemotherapy in Subjects With Locally Advanced or Metastatic Urothelial Cancer Who Have Previously Received PD- (L)1 Inhibitor and Platinum-containing Chemotherapy    Click to Show/Hide
Undisclosed	NCT06551233	PHASE1	A Clinical Study on the Safety and Efficacy of 9MW2821 in Patients With High-risk Non-muscle-invasive Bladder Cancer (NMIBC) That Have Previously Failed to Intravesical Therapy
Undisclosed	NCT06592326	PHASE3	A Randomized, Controlled, Open-label, Multicenter Phase 3 Clinical Study of 9MW2821 in Combination With Toripalimab Versus Standard Chemotherapy in First-line Locally Advanced or Metastatic Urothelial Cancer    Click to Show/Hide
Undisclosed	NCT06823427	PHASE2	A Randomized Phase II Trial to Evaluate 9MW2821 in Combination With Toripalimab Compared With 9MW2821 Monotherapy for the 1st Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Objective Response Rate (ORR)	38.50%
Patients Enrolled	Eligible patients (18-80 years, ECOG 0-1) must have advanced solid tumors (excluding sarcoma, with Nectin-4 testing in expansion cohorts), measurable disease (RECIST 1.1), and adequate organ function. Exclusions: recent anticancer therapies/surgeries (within 14-28 days), prior MMAE/nectin-4 ADCs, uncontrolled comorbidities (CNS metastases, diabetes, neuropathy ≥Grade 2), or CYP3A4/P-gp modifiers within 14 days. Contraception is mandatory during and for 6 months post-study    Click to Show/Hide
Administration Dosage	All subjects will receive a single intravenous (IV) infusion of 9MW2821 once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).
Related Clinical Trial
NCT Number	NCT05216965	Clinical Status	PHASE1|||PHASE2
Clinical Description	Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
Primary Endpoint	The primary safety outcome is adverse event incidence assessed until 28 days post-treatment, while the Phase 2 efficacy endpoint is confirmed objective response rate (ORR ≥28 days) evaluating complete/partial responses over 24 months.
Other Endpoint	Key secondary endpoints include pharmacokinetics (Cmax, AUC, t½, CL) for TAb/ADC/MMAE, along with disease control rate, duration of response, time to response, progression-free survival, overall survival (all 24-month assessments), and anti-drug antibody monitoring.
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Disease control rate (DCR)	84.60%
Patients Enrolled	Eligible patients (18-80 years, ECOG 0-1) must have advanced solid tumors (excluding sarcoma, with Nectin-4 testing in expansion cohorts), measurable disease (RECIST 1.1), and adequate organ function. Exclusions: recent anticancer therapies/surgeries (within 14-28 days), prior MMAE/nectin-4 ADCs, uncontrolled comorbidities (CNS metastases, diabetes, neuropathy ≥Grade 2), or CYP3A4/P-gp modifiers within 14 days. Contraception is mandatory during and for 6 months post-study    Click to Show/Hide
Administration Dosage	All subjects will receive a single intravenous (IV) infusion of 9MW2821 once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).
Related Clinical Trial
NCT Number	NCT05216965	Clinical Status	PHASE1|||PHASE2
Clinical Description	Phase I/II Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
Primary Endpoint	The primary safety outcome is adverse event incidence assessed until 28 days post-treatment, while the Phase 2 efficacy endpoint is confirmed objective response rate (ORR ≥28 days) evaluating complete/partial responses over 24 months.
Other Endpoint	Key secondary endpoints include pharmacokinetics (Cmax, AUC, t½, CL) for TAb/ADC/MMAE, along with disease control rate, duration of response, time to response, progression-free survival, overall survival (all 24-month assessments), and anti-drug antibody monitoring.
Experiment 3 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Eligible patients (18-75 years) must have ECOG 0-1, measurable disease (RECIST v1.1), adequate organ function, and ≥12-week life expectancy. Key exclusions: Grade ≥2 treatment-related toxicities or peripheral neuropathy; active autoimmune diseases; recent anticancer therapies (chemotherapy/radiotherapy within 21 days or immunotherapy within 14 days); prior nectin-4 targeted ADC treatment; major surgery within 28 days; significant cardiac/cerebrovascular events within 6 months; or other active malignancies within 3 years. Contraception is required during and for 6 months post-treatment.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT06492005	Clinical Status	PHASE2
Clinical Description	A Phase II Clinical Study of Efficacy and Safety of 9MW2821Monotherapy or Combined With PD-1 Inhibitor in Locally Advanced or Metastatic Triple-Negative Breast Cancer
Primary Endpoint	The primary efficacy endpoint is objective response rate (ORR) according to RECIST v1.1, evaluated over a 24-month period in patients with locally advanced or metastatic triple-negative breast cancer.
Other Endpoint	Secondary outcomes include duration of response (DoR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) all assessed over 24 months. Pharmacokinetic analysis will measure Cmax, AUC, t1/2, and CL of TAb, ADC, and MMAE. Anti-drug antibody (ADA) incidence will be monitored throughout the study period.    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	Eligible patients must have ECOG 0-1, ≥12-week life expectancy, measurable disease (RECIST v1.1), and ≤2 prior systemic therapies (including platinum-based chemo ± bevacizumab). Exclusions: non-HPV-associated histologies, recent anticancer treatments (chemotherapy/radiation within 21 days; investigational drugs within 28 days), Grade ≥2 toxicity, uncontrolled comorbidities (HbA1c ≥8%, active infections, CNS metastases), major surgery within 28 days, or prior nectin-4/MMAE-based ADCs. Contraception is required during and for 6 months post-study.    Click to Show/Hide
Administration Dosage	1.25mg/kg of 9MW2821 by intravenous infusion on days 1, 8 and 15 of every 28-day cycle
Related Clinical Trial
NCT Number	NCT06692166	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-label, Phase 3 Study to Evaluate 9MW2821 vs Treatment of Physician's Choice in Subjects With Recurrent or Metastatic Cervical Cancer Who Progressed on or After Platinum-based Chemotherapy
Primary Endpoint	The primary endpoint is overall survival (OS), defined as the time from randomization to death from any cause, assessed over a 3-year study period in female patients (18-75 years) with recurrent/metastatic cervical cancer.
Other Endpoint	Secondary efficacy endpoints include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and time to response (TTR), all investigator-assessed per RECIST v1.1 over 3 years. Safety endpoints cover adverse event incidence and anti-drug antibody (ADA) development.
Experiment 5 Reporting the Activity Date of This ADC					[6]
Patients Enrolled	Eligible patients (18-80 years, ECOG 0-1) must have advanced solid tumors (Phase Ia) or metastatic UC (Phase Ib), prior ICI/GC/GP therapy exposure, measurable disease (RECIST 1.1), adequate organ function, and provide tumor samples. Exclusions: recent anticancer therapies/surgeries (14-28 days), Grade ≥2 toxicity/neuropathy, MMAE-ADC treatment, uncontrolled comorbidities (CNS metastases, diabetes, cardiovascular disease), or strong CYP3A4/P-gp modifiers within 14 days. Contraception is mandatory during and 6 months post-study.    Click to Show/Hide
Administration Dosage	All subjects will receive a single intravenous (IV) infusion of 9MW2821 once weekly for the first 3 weeks of every 4 week cycle (i.e., on Days 1, 8 and 15).
Related Clinical Trial
NCT Number	NCT05773937	Clinical Status	PHASE1
Clinical Description	A Phase I Clinical Study of the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of 9MW2821 in Advanced Malignant Solid Tumors
Primary Endpoint	The primary safety endpoint evaluates adverse event incidence monitored up to 28 days after the last dose administration.
Other Endpoint	Key secondary endpoints include PK parameters (Cmax, AUC, t1/2, CL for TAb/ADC/MMAE) and efficacy measures (ORR, DCR, DoR, TTR, PFS, OS) over 24 months, alongside anti-drug antibody (ADA) incidence assessment.
Experiment 6 Reporting the Activity Date of This ADC					[7]
Patients Enrolled	Eligible participants (18-80 years, ECOG 0-1) must have histologically confirmed locally advanced/metastatic urothelial cancer, prior standard therapy (or treatment-naïve), measurable lesions (RECIST 1.1), adequate organ function, and tumor tissue availability. Exclusions encompass recent anticancer treatments (within 21 days), prior MMAE-ADC/PD- (L)1 therapy, significant treatment-related toxicity (≥Grade 2), uncontrolled comorbidities (CNS metastases, infections, diabetes), major surgery (within 28 days), strong CYP3A4/P-gp modifiers (14 days), active corneal risks, or conditions posing significant safety concerns. Contraception is required during and for 6 months post-study.    Click to Show/Hide
Administration Dosage	1.0/1.25/1.5 mg/kg, intravenous (IV) infusion every cycle until disease progression or intolerable toxicity, etc.
Related Clinical Trial
NCT Number	NCT06079112	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Phase Ib/II, Open-label, Single Arm, Multicenter Clinical Study to Evaluate the Safety and Efficacy of 9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer
Primary Endpoint	The primary safety endpoints include incidence rates of adverse events (AEs) and serious adverse events (SAEs), monitored continuously throughout the study period of up to 24 months.
Other Endpoint	The key efficacy assessments consist of Objective Response Rate (ORR), Duration of Response (DOR), Time to Response (TTR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS), all evaluated over a 24-month timeframe; additional PK parameters (9MW2821 concentration) and immunogenicity (ADA) data will be collected for up to 12 months.    Click to Show/Hide
Experiment 7 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Eligible subjects (18-75 years, ECOG 0-1) must have locally advanced/metastatic urothelial cancer (platinum/PD- (L)1-refractory), measurable disease (RECIST 1.1), and adequate organ function. Exclusions: recent anticancer therapies (21 days), prior nectin-4/MMAE-ADC treatment, major surgery (28 days), Grade ≥2 toxicity/neuropathy, uncontrolled comorbidities (CNS metastases, HbA1c ≥8%, cardiac/cerebrovascular disease within 6 months), strong CYP3A4 modifiers (14 days), active infections, or conditions posing safety risks. Contraception is mandatory during and post-study (6 months).    Click to Show/Hide
Administration Dosage	1.25mg/kg of 9MW2821 by intravenous infusion on days 1, 8 and 15 of every 28-day cycle
Related Clinical Trial
NCT Number	NCT06196736	Clinical Status	PHASE3
Clinical Description	An Open-label, Randomized Phase 3 Study to Evaluate 9MW2821 vs Investigator's Choice of Chemotherapy in Subjects With Locally Advanced or Metastatic Urothelial Cancer Who Have Previously Received PD- (L)1 Inhibitor and Platinum-containing Chemotherapy
Primary Endpoint	Primary efficacy endpoints include Progression-Free Survival (PFS) and Overall Survival (OS), assessed via Blinded Independent Central Review (BICR) over 3 years, measuring time from randomization to disease progression or death (PFS) and time until death from any cause (OS).
Other Endpoint	Secondary endpoints evaluated over 3 years encompass Objective Response Rate (ORR), Duration of Response (DOR), Time to Response (TTR), Disease Control Rate (DCR) per BICR/investigator, plus investigator-assessed PFS, alongside safety metrics (AE/ADA incidence) and quality-of-life measures (EORTC QLQ-C30, EQ-5D-5L VAS changes from baseline).
Experiment 8 Reporting the Activity Date of This ADC					[9]
Patients Enrolled	Eligible participants (≥18 years) must have high-risk NMIBC (non-muscle invasive, BCG/gemcitabine-refractory) post-TURBT (within 6 weeks), ECOG 0-1, and adequate organ function. Exclusions: prior muscle-invasive/metastatic disease, recent anticancer therapies (3 weeks), unresolved toxicity (>Grade 1), active infections, cardiovascular events (6 months), Nectin-4/MMAE-ADC exposure, or positive HBV/HCV/HIV serology. Contraception is mandatory during and for 180 days post-treatment.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT06551233	Clinical Status	PHASE1
Clinical Description	A Clinical Study on the Safety and Efficacy of 9MW2821 in Patients With High-risk Non-muscle-invasive Bladder Cancer (NMIBC) That Have Previously Failed to Intravesical Therapy
Primary Endpoint	The study will evaluate safety and tolerability over 12 months by assessing AE/SAE incidence while determining the Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) to establish safe dosing parameters.
Other Endpoint	Efficacy assessments include 12-month Disease-Free Survival (DFS) rate, Duration of Complete Response (DoR), CR rates at 3/6/12 months, long-term DFS (up to 20 months), time to/proportion of radical cystectomy, and biomarker analysis (Nectin-4 expression).
Experiment 9 Reporting the Activity Date of This ADC					[10]
Patients Enrolled	Eligible participants (18-80 years, ECOG 0-1) must have untreated locally advanced/metastatic urothelial cancer (RECIST v1.1-measurable, cisplatin/carboplatin-suitable), adequate organ function, and accessible tumor tissue. Exclusions: prior malignancies (3 years), autoimmune/cardiovascular conditions (6 months), recent therapies (surgery/radiotherapy/CYP3A4 modulators), Grade ≥2 residual toxicity (excluding alopecia), active infections, Nectin-4/MMAE-ADC or checkpoint inhibitor exposure, uncontrolled CNS metastases, HBV/HCV/HIV coinfection, drug allergies, or high-risk ocular/neurological conditions. Contraception and protocol compliance are mandatory.    Click to Show/Hide
Administration Dosage	9MW2821, 1.25mg/kg, intravenous (IV) infusion
Related Clinical Trial
NCT Number	NCT06592326	Clinical Status	PHASE3
Clinical Description	A Randomized, Controlled, Open-label, Multicenter Phase 3 Clinical Study of 9MW2821 in Combination With Toripalimab Versus Standard Chemotherapy in First-line Locally Advanced or Metastatic Urothelial Cancer
Primary Endpoint	The primary endpoints include Blinded Independent Central Review-assessed Progression-Free Survival (BICR-PFS) and Overall Survival (OS), both evaluated over a 50-month timeframe.
Other Endpoint	Secondary outcomes comprise Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Response (DoR), investigator-assessed PFS, safety metrics (AE/SAE), and immunogenicity (Anti-Drug Antibodies against 9MW2821), all monitored for up to 50 months.
Experiment 10 Reporting the Activity Date of This ADC					[11]
Patients Enrolled	Eligible patients (18-80 years, ECOG 0-1) must have untreated, histologically confirmed inoperable locally advanced/metastatic urothelial carcinoma (>50% urothelial differentiation) with ≥1 measurable lesion (RECIST v1.1). Key exclusions: other malignancies (3 years), active autoimmune disease requiring immunosuppressants, recent major cardiovascular/thromboembolic events (6 months), prior PD-1/PD-L1/CTLA-4/Nectin-4/MMAE-ADC therapy, uncontrolled infections, untreated CNS metastases, positive HBV/HCV/HIV serology, or drug allergies. Contraception and protocol adherence are mandatory.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT06823427	Clinical Status	PHASE2
Clinical Description	A Randomized Phase II Trial to Evaluate 9MW2821 in Combination With Toripalimab Compared With 9MW2821 Monotherapy for the 1st Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma
Primary Endpoint	The primary endpoint is Objective Response Rate (ORR) assessed by Blinded Independent Central Review (BICR) over a 3-year period.
Other Endpoint	Secondary efficacy assessments include Overall Survival (OS), Progression-Free Survival (PFS), Duration of Response (DoR), Disease Control Rate (DCR), and ORR (investigator- and BICR-assessed). Safety monitoring covers treatment-emergent and -related adverse events (CTCAE v5.0), serious adverse events, and vital/lab abnormalities. Immunogenicity analysis measures ADA/NAb incidence, rates, and titers over 3 years.    Click to Show/Hide

Ref 1	Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E-based Antibody-Drug Conjugate for Treatment of Nectin-4-expressing Cancers
Ref 2	Development and validation of bioanalytical assays for the quantification of 9MW2821, a nectin-4-targeting antibody-drug conjugate
Ref 3	A Clinical Study of 9MW2821 in Subjects With Advanced Malignant Solid Tumors
Ref 4	A Clinical Study of 9MW2821 (and PD-1 Inhibitor) in Locally Advanced or Metastatic Triple-Negative Breast Cancer
Ref 5	A Study to Evaluate 9MW2821 Versus Treatment of Physician's Choice for Subjects With Recurrent or Metastatic Cervical Cancer
Ref 6	A Clinical Study of 9MW2821 in Advanced Malignant Solid Tumors
Ref 7	9MW2821 Combined With Toripalimab Injection in Subjects With Local Advanced or Metastatic Urothelial Cancer
Ref 8	A Study to Evaluate 9MW2821 Versus Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Ref 9	Safety and Efficacy of 9MW2821 in the Treatment of High-risk Non-muscle-invasive Bladder Cancer (NMIBC)
Ref 10	9MW2821 in Combination With Toripalimab vs Standard Chemotherapy in Locally Advanced or Metastatic Urothelial Cancer
Ref 11	9MW2821 + Toripalimab vs 9MW2821 for 1st Line Locally Advanced or Metastatic Urothelial Carcinoma