Linker Information

General Information of This Linker

Linker ID	LIN0LWOKO
Linker Name	NH2-PEG3-Val-Cit-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
Structure	3D MOL		2D MOL
Formula	C26H44N6O8
Isosmiles	OCC(C=C1)=CC=C1NC([C@@H](NC([C@H](C(C)C)NC(COCCOCCOCCN)=O)=O)CCCNC(N)=O)=O
InChI	InChI=1S/C26H44N6O8/c1-18(2)23(32-22(34)17-40-15-14-39-13-12-38-11-9-27)25(36)31-21(4-3-10-29-26(28)37)24(35)30-20-7-5-19(16-33)6-8-20/h5-8,18,21,23,33H,3-4,9-17,27H2,1-2H3,(H,30,35)(H,31,36)(H,32,34)(H3,28,29,37)/t21-,23-/m0/s1
InChIKey	FSVRVIFMHZBDGT-GMAHTHKFSA-N
Pharmaceutical Properties	Molecule Weight	568.672	Polar area	216.36
	Complexity	848.5294342	xlogp Value	-0.8
	Heavy Count	40	Rot Bonds	21
	Hbond acc	9	Hbond Donor	7

Each Antibody-drug Conjugate Related to This Linker

Full Information of The Activity Data of The ADC(s) Related to This Linker

Trastuzumab envedotin [Phase 3]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 14 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
*Related Clinical Trial*
NCT Number	NCT04826107	Clinical Status	Phase 2
Clinical Description	An open-label, multicentre, phase 2 study of DP303c injection in patients with unresectable locally advanced, recurrent or metastatic gastric cancer with HER2 expression.
Experiment 2 Reporting the Activity Date of This ADC				[2]
*Related Clinical Trial*
NCT Number	NCT04828616	Clinical Status	Phase 2
Clinical Description	An open-label, multicentre, phase 2 study of DP303c injection in patients with HER2-expressing advanced ovarian cancer.
Experiment 3 Reporting the Activity Date of This ADC				[3]
*Related Clinical Trial*
NCT Number	NCT05334810	Clinical Status	Phase 2
Clinical Description	A multi-center, open-lable, single-arm phase 2 study to evaluate the efficacy and safety of DP303c in patients with HER2-positive unresectable locally advanced, relapsed, or metastatic breast cancer.
Experiment 4 Reporting the Activity Date of This ADC				[4]
*Related Clinical Trial*
NCT Number	NCT04146610	Clinical Status	Phase 1
Clinical Description	A phase 1a, multicenter, open and dose-increasing study of DP303c to evaluate the safety , pharmacokinetics, immunogenicity and antitumor activity of subjects with HER2-positive advanced solid tumors.
Experiment 5 Reporting the Activity Date of This ADC				[6]
Efficacy Data	Tumor-associated calcium signal transducer 2 (TACSTD2)	. . .
Patients Enrolled	Eligibility requires age ≥18 with ECOG 0-1, HER2+ advanced solid tumors, prior anti-HER2 therapy, and adequate organ function. Key exclusions: LVEF<40%, grade ≥3 neuropathy, active hepatitis/HIV, recent CYP3A modulators (14 days), anthracycline overexposure, or uncontrolled CNS metastases. Contraception mandated for 6 months post-treatment.
Administration Dosage	DP303c injection, 3.0 mg/kg, every 3 weeks.
*Related Clinical Trial*
NCT Number	NCT05810103	Clinical Status	PHASE1
Clinical Description	A Multi-center, Single-arm, Phase I Study of DP303c in Patients With HER2-positive Advanced Solid Tumors
Primary Endpoint	Primary pharmacokinetic endpoints include Cmax, AUC0-last, AUC0-inf, and Tmax of the investigational drug measured during multiple dosing cycles (21-day cycles) in patients with HER2-positive advanced solid tumors.
Other Endpoint	Secondary endpoints assess safety (AE incidence over 12 months), efficacy (ORR, DCR, DoR over 12 months), and immunogenicity (ADA/Nab incidence measured during treatment cycles) in this phase I clinical trial.
Experiment 6 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Progression Free Survival	4.44 months
Patients Enrolled	Inclusion: HER2+ (IHC2+/ISH+ or IHC3+) advanced solid tumor patients aged 18-75 with ECOG 0-1, adequate organ function, measurable disease. Exclusion: Active CNS metastases, LVEF<40%, ≥Grade 2 neuropathy, uncontrolled cardiac/electrolyte disorders, active hepatitis/HIV, recent CYP3A modulators (14 days), or anthracycline exposure ≥360mg/m2 doxorubicin equivalent. Contraception required for 12 weeks post-treatment. Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT04146610	Clinical Status	PHASE1
Clinical Description	A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors
Primary Endpoint	Primary endpoint is MTD determination of DP303c during the first 21-day cycle, defined as the highest dose where <2/6 patients experience DLT in advanced HER2+ solid tumors.
Other Endpoint	Secondary endpoints include PK parameters (Cmax, Tmax, AUC over 2 years), preliminary efficacy (ORR, DoR), and immunogenicity (ADA incidence) in this Phase I study.
Experiment 7 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Objective Response Rate (ORR)	42.90%
Patients Enrolled	Inclusion: HER2+ (IHC2+/ISH+ or IHC3+) advanced solid tumor patients aged 18-75 with ECOG 0-1, adequate organ function, measurable disease. Exclusion: Active CNS metastases, LVEF<40%, ≥Grade 2 neuropathy, uncontrolled cardiac/electrolyte disorders, active hepatitis/HIV, recent CYP3A modulators (14 days), or anthracycline exposure ≥360mg/m2 doxorubicin equivalent. Contraception required for 12 weeks post-treatment. Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT04146610	Clinical Status	PHASE1
Clinical Description	A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors
Primary Endpoint	Primary endpoint is MTD determination of DP303c during the first 21-day cycle, defined as the highest dose where <2/6 patients experience DLT in advanced HER2+ solid tumors.
Other Endpoint	Secondary endpoints include PK parameters (Cmax, Tmax, AUC over 2 years), preliminary efficacy (ORR, DoR), and immunogenicity (ADA incidence) in this Phase I study.
Experiment 8 Reporting the Activity Date of This ADC				[7]
Efficacy Data	Disease control rate (DCR)	68.10%
Patients Enrolled	Inclusion: HER2+ (IHC2+/ISH+ or IHC3+) advanced solid tumor patients aged 18-75 with ECOG 0-1, adequate organ function, measurable disease. Exclusion: Active CNS metastases, LVEF<40%, ≥Grade 2 neuropathy, uncontrolled cardiac/electrolyte disorders, active hepatitis/HIV, recent CYP3A modulators (14 days), or anthracycline exposure ≥360mg/m2 doxorubicin equivalent. Contraception required for 12 weeks post-treatment. Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT04146610	Clinical Status	PHASE1
Clinical Description	A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors
Primary Endpoint	Primary endpoint is MTD determination of DP303c during the first 21-day cycle, defined as the highest dose where <2/6 patients experience DLT in advanced HER2+ solid tumors.
Other Endpoint	Secondary endpoints include PK parameters (Cmax, Tmax, AUC over 2 years), preliminary efficacy (ORR, DoR), and immunogenicity (ADA incidence) in this Phase I study.
Experiment 9 Reporting the Activity Date of This ADC				[8]
Patients Enrolled	Inclusion: HER2+ breast cancer patients (IHC 3+ or IHC 2+/ISH+) aged 18-75 with ≥2 prior anti-HER2 lines (including trastuzumab), measurable disease, ECOG 0-1, LVEF≥50%, and adequate organ function. Exclusion: Prior DP303c treatment, active CNS metastases, LVEF<40% history, uncontrolled comorbidities, recent anticancer therapies (4w chemo/2w endocrine), active infections (HBV/HCV), or CYP3A modulator use within 14 days. Contraception required for 6 months post-treatment. Click to Show/Hide
Administration Dosage	DP303c injection, 3.0 mg/kg, every 3 weeks.
*Related Clinical Trial*
NCT Number	NCT05334810	Clinical Status	PHASE2
Clinical Description	A Multi-center, Open-lable, Single-arm Phase II Study to Evaluate the Efficacy and Safety of DP303c in Patients With HER2-positive Unresectable Locally Advanced, Relapsed, or Metastatic Breast Cancer
Primary Endpoint	Primary endpoint is ORR assessed by IRC per RECIST v1.1 with tumor evaluations every 6 weeks from baseline.
Other Endpoint	Secondary endpoints include DOR and PFS measured at 6-week intervals from baseline until progression.
Experiment 10 Reporting the Activity Date of This ADC				[9]
Patients Enrolled	Inclusion: HER2+ breast cancer patients (IHC 3+/ISH+) aged ≥18 with ≥2 prior systemic therapies, measurable disease, ECOG 0-1, adequate organ function. Exclusion: Pregnancy, recent anticancer treatments (28d systemic/14d TCM therapy), active CNS metastases, LVEF<40%, severe comorbidities (cardiopulmonary/neuropathic/ocular), active infections (HBV/HCV/HIV), or CYP3A modulator use. Contraception required during study participation. Click to Show/Hide
Administration Dosage	Eligible patients will be treated with trastuzumab IV on day 1 and oral capecitabine twice daily on days 1-14 every 3 weeks, or patients will be treated with trastuzumab IV on day 1 and vinorelbine IV over on days 1 and 8 every 3 weeks.
*Related Clinical Trial*
NCT Number	NCT05901935	Clinical Status	PHASE3
Clinical Description	A Multicentre, Randomized, Open-label, Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of DP303cversus Trastuzumab Combined With Vinorelbine/Capecitabine in of HER2-positive Advanced Breast Cancer
Primary Endpoint	Primary endpoint is PFS assessed by BIRC per RECIST v1.1 with follow-up up to 5 years.
Other Endpoint	Secondary endpoints include investigator-assessed PFS, OS, ORR, DoR (all evaluated per RECIST v1.1 over 5 years), and AE incidence/severity monitoring throughout the study period.
Experiment 11 Reporting the Activity Date of This ADC				[10]
Patients Enrolled	Inclusion: HER2+ (IHC3+/ISH+) breast cancer patients ≥18 years with prior trastuzumab/taxane treatment, ECOG 0-2, adequate organ function. Exclusion: Prior HER2-ADC therapy, active CNS metastases, uncontrolled effusions, Grade≥2 neuropathy, recent anticancer therapies (4w immunotherapy/2w chemotherapy), ocular/cardiopulmonary comorbidities, or active infections requiring IV treatment. Click to Show/Hide
Administration Dosage	DP303c injection, 3.0 mg/kg, Q3W.
*Related Clinical Trial*
NCT Number	NCT06313086	Clinical Status	PHASE3
Clinical Description	A Multicentre, Randomized, Open-label, Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of DP303c Versus Trastuzumab Emtansine in Patients With HER2-positive Advanced Breast Cancer
Primary Endpoint	Primary endpoint is BIRC-assessed PFS per RECIST v1.1 with 4-year follow-up in HER2+ advanced/metastatic breast cancer patients.
Other Endpoint	Secondary endpoints include investigator-assessed PFS, OS, ORR, DoR (all per RECIST v1.1) and AE monitoring over 4 years, evaluating both efficacy and safety outcomes.
Experiment 12 Reporting the Activity Date of This ADC				[11]
Patients Enrolled	Eligibility requires age 18-75 with progressed gastric cancer after 1-2 prior therapies (including platinum/fluorouracil), measurable lesions, and organ function adequacy. Key exclusions: trastuzumab intolerance, uncontrolled effusions, active CNS metastases, ≥Grade 2 neuropathy, recent CYP3A4/UGT1A1 modulator use, or significant ocular/cardiovascular comorbidities. Click to Show/Hide
Administration Dosage	DP303c injection, dose level 1, intravenous drip, Q3W + simmitinib tablets, dose level 1, oral, QD, taken for 3 weeks, discontinued for 1 week, Q4W
*Related Clinical Trial*
NCT Number	NCT06577376	Clinical Status	PHASE1\|\|\|PHASE2
Clinical Description	A Multicenter, Open-label Phase I/II Clinical Study to Evaluate the Safety and Efficacy of Simmitinib or Irinotecan Liposomes Combined With DP303c Injection in the Treatment of HER2 Expressing Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Primary Endpoint	Primary endpoints include DLT occurrence/incidence, AE/SAE monitoring, and ORR per RECIST 1.1 assessed over 36 months in HER2-positive (IHC 1+/2+/3+) gastric/GEJ adenocarcinoma patients.
Other Endpoint	Secondary outcomes comprise efficacy measures (DCR, DoR, PFS, OS) and pharmacokinetic evaluations (DP303c/simmitinib concentrations, ADA incidence, HER2 expression) tracked for 36 months.
Experiment 13 Reporting the Activity Date of This ADC				[12]
Patients Enrolled	Inclusion: Age 18-75 with histologically confirmed advanced gastric cancer, ECOG 0-1, adequate organ function, measurable lesions (RECIST v1.1), and progression after platinum/taxane-based therapy (HER2-positive cohorts require prior trastuzumab). Exclusion: Active CNS metastases, uncontrolled effusions, ≥Grade 2 neuropathy, cardiac dysfunction (LVEF<50%), recent CYP3A4 modulators, or prior HER2-ADC therapy. Contraception required for 6 months post-treatment. Click to Show/Hide
Administration Dosage	Patients with HER2-positive advanced or metastatic gastric cancer after receiving 1st-line treatment will be treated with DP303c injection at 2.0 mg/kg,2.5 mg/kg or 3.0 mg/kg every 3 weeks to determine the recommended dose.
*Related Clinical Trial*
NCT Number	NCT04826107	Clinical Status	PHASE2
Clinical Description	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Gastric Cancer With HER2 Expression
Primary Endpoint	Primary endpoint is ORR (CR+PR rate) assessed over 2.5 years in HER2-positive/low-expression gastric/GEJ adenocarcinoma patients with progression after ≥1 prior therapy.
Other Endpoint	Secondary endpoints include PFS, OS, DCR, DoR (all measured over 2.5 years) and AE/SAE monitoring, evaluating both efficacy and safety outcomes in this multicenter trial.
Experiment 14 Reporting the Activity Date of This ADC				[13]
Patients Enrolled	Inclusion: Women aged 18-75 with ECOG 0-2, measurable lesions (RECIST v1.1), adequate organ function, and HER2 IHC 1+/2+/3+ status. Exclusion: Active CNS metastases, ≥Grade 2 neuropathy, LVEF<50%, uncontrolled effusions, recent CYP3A4 modulators (28 days), prior HER2-ADC therapy, or anthracycline exposure >500mg/m2 doxorubicin equivalent. Contraception required for 6 months post-treatment. Click to Show/Hide
Administration Dosage	Part1:Patients with HER2-expressing advanced ovarian cancer will be treated with DP303c injection at 2.0 mg/kg or 3.0 mg/kg every 3 weeks (Q3W) to determine the recommended phase 2 dose (RP2D).Part2a:Patients with HER2-overexpressing advanced ovarian cancer will be treated with DP303c injection at RP2D.Part2b:Patients with HER2-lowexpressing advanced ovarian cancer will be treated with DP303c injection at RP2D. Click to Show/Hide
*Related Clinical Trial*
NCT Number	NCT04828616	Clinical Status	PHASE2
Clinical Description	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With HER2-expressing Advanced Ovarian Cancer
Primary Endpoint	Primary endpoint is ORR (CR+PR rate) assessed over 3 years in HER2-positive/low-expressing ovarian/tubal/peritoneal cancer patients with prior platinum therapy.
Other Endpoint	Secondary endpoints include PFS, OS, DoR (3-year follow-up), AE/SAE monitoring (NCI-CTCAE v5.0), PK parameters (Cmax/Tmax/AUC of DP303c), and ADA incidence in this phase I/II study.

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 34 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 7.60%	Moderate HER2 expression (HER2++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 16.20%	Moderate HER2 expression (HER2++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 28.47%	High HER2 expression (HER2+++/++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 33.60%	High HER2 expression (HER2+++/++)
Method Description	DP001 (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 39%	Moderate HER2 expression (HER2++)
Method Description	DP303c (0.3 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.26%	High HER2 expression (HER2+++/++)
Method Description	DP303c (1 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 54.40%	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 0.1 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.10%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 1 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83.94%	High HER2 expression (HER2+++/++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 10 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.48%	High HER2 expression (HER2+++/++)
Method Description	DP001 (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 11 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 91.60%	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 12 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94%	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 13 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94%	High HER2 expression (HER2+++/++)
Method Description	DP303c (5 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 14 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94%	High HER2 expression (HER2+++/++)
Method Description	DP303c (2.5 mg/kg).
In Vivo Model	NCI-N87 xenograft model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 15 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.10%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 16 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.16%	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 17 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.30%	High HER2 expression (HER2+++/++)
Method Description	T-DM1 (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 18 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97%	High HER2 expression (HER2+++/++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 19 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97%	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 20 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97%	High HER2 expression (HER2+++/++)
Method Description	DP303c (15 mg/kg).
In Vivo Model	HCC1954 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 21 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.10%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 22 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.50%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 23 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.50%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 2.5 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 24 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80%	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 1 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 25 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 26 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.80%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 5 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 27 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.50%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 28 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.54%	High HER2 expression (HER2+++/++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	SK-OV-3 cell line xenograft model
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 29 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.80%	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 3 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 30 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.10%	High HER2 expression (HER2+++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 15 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 31 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.90%	Moderate HER2 expression (HER2++)
Method Description	Pathogen-free female nude mice were injected subcutaneously with each cell suspension. According to tumor volumes,the mice were randomly divided in two groups: treatment and control groups. Each drug was given to the animals intravenously. The dosing frequency was once a week (qw), qw 2 or qw 3.DP303c induced obvious tumor growth inhibition at a single dose of 10 mg/kg. Click to Show/Hide
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 32 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate HER2 expression (HER2++)
Method Description	DP303c (10 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 33 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate HER2 expression (HER2++)
Method Description	DP303c (3 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 34 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate HER2 expression (HER2++)
Method Description	DP303c (1 mg/kg).
In Vivo Model	JIMT -1 cell line xenograft model
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Revealed Based on the Cell Line Data

Click To Hide/Show 14 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	Moderate HER2 expression (HER2++; HER2 MFI=157,231)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.07 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	High HER2 expression (HER2+++; HER2 MFI=987,353)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.08 nM	Negative HER2 expression (HER2-; HER2 MFI=256)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Invasive breast carcinoma	BT-474 cells		CVCL_0179
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	High HER2 expression (HER2+++)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast ductal carcinoma	HCC1954 cells		CVCL_1259
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.22 nM	Negative HER2 expression (HER2-)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.22 nM	High HER2 expression (HER2+++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.23 nM	High HER2 expression (HER2+++; HER2 MFI=804,573)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 10 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.23 nM	High HER2 expression (HER2+++; HER2 MFI=892,333)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1 x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1 x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 11 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.39 nM	High HER2 expression (HER2+++)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 12 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.39 nM	Moderate HER2 expression (HER2++)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 13 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 50 nM	High HER2 expression (HER2+++; HER2 MFI=1,106,494)
Method Description	To obtain a single-cell suspension, the cells were harvested and resuspended. The cell density was adjusted to 1x10⁵ cells/mL and seeded in a 96-well cell culture plate at 100 uL/well (1x10⁴ cells/well). DP303c labeled with DyLight 488 was added into the 96-well plate with a final concentration of 2 ug/mL.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 14 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000 nM	High HER2 expression (HER2+++; HER2 MFI=765,629)
Method Description	Comparison of in vitro Activity Between DP303c and T -DM1 in Variable HER2 Cell Lines.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419

SYS6002 [Phase 3]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[14]
Patients Enrolled	Key eligibility: Inclusion requires nectin-4+ advanced/metastatic solid tumors with ≥1 prior therapy failure; Exclusion criteria cover active CNS metastases, grade≥2 neuropathy, uncontrolled diabetes (HbA1c≥8%), ocular/liver/pulmonary diseases, and significant comorbidities.
Administration Dosage	CRB-701 Dose level 1, intravenous infusion over 30 mins, Dose schedule 1
*Related Clinical Trial*
NCT Number	NCT06265727	Clinical Status	PHASE1\|\|\|PHASE2
Clinical Description	A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics, and Efficacy of CRB-701, an Antibody-drug Conjugate Targeting Nectin-4, in Patients with Advanced Solid Tumors
Primary Endpoint	Primary endpoints include MTD/PADR determination via DLT assessment in Part A (21-day window) and efficacy evaluation through DCR (CR+PR+SD≥4 months) and ORR (CR+PR per RECIST 1.1) in Parts B&C (6-month follow-up).
Other Endpoint	Secondary objectives cover safety profiling (TEAEs by CTCAE v5.0) across all phases and PK analysis (9-week duration) of CRB-701 components including total ADC/free MMAE/total antibody parameters (Cmax/Tmax/AUC) for single/multiple dosing.

References

Ref 1	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With Unresectable Locally Advanced, Recurrent or Metastatic Gastric Cancer With HER2 Expression, NCT04826107
Ref 2	An Open-label, Multicentre, Phase II Study of DP303c Injection in Patients With HER2-expressing Advanced Ovarian Cancer, NCT04828616
Ref 3	A Multi-center, Open-lable, Single-arm Phase II Study to Evaluate the Efficacy and Safety of DP303c in Patients With HER2-positive Unresectable Locally Advanced, Relapsed, or Metastatic Breast Cancer, NCT05334810
Ref 4	A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors, NCT04146610
Ref 5	An Innovative Site-Specific Anti-HER2 Antibody-Drug Conjugate with High Homogeneity and Improved Therapeutic Index. Onco Targets Ther. 2022 Apr 8;15:331-343.
Ref 6	A Study of DP303c in Patients With HER2-positive Advanced Solid Tumors
Ref 7	Study of DP303c Administered Intravenously to Subjects With HER2-Positive in Advanced Solid Tumors
Ref 8	DP303c in Patients With HER2-positive Unresectable Locally Advanced, Relapsed, or Metastaticbreast Cancer
Ref 9	DP303c in Patients With HER2-positive Advanced Breast Cancer
Ref 10	DP303c Versus Trastuzumab Emtansine in in Patients With HER2-positive Advanced Breast Cancer
Ref 11	A PhaseI/II Study of Simmitinib or Irinotecan Liposomes Combined With DP303c in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Ref 12	Study of DP303c Injection in Patients With Advanced or Metastatic Gastric Cancer
Ref 13	Study of DP303c Injection in Patients With Advanced Ovarian Cancer
Ref 14	A Phase 1/2 Study to Investigate CRB-701 in Solid Tumors

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)