ADC ID	DRG0THGAW
ADC Name	Trastuzumab duocarmazine
Synonyms	trastuzumab duocarmazine; trastuzumab vc-seco-DUBA; SYD985; (vic-)trastuzumab duocarmazine; Jivadco; T-Duo    Click to Show/Hide
Organization	Byondis (Originator);medac
Drug Status	New Drug Application (discontinued)
Drug-to-Antibody Ratio	2.8
Structure
	3D MOL			2D MOL
Antibody Name	Trastuzumab					Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (HER2 ECD2); Receptor tyrosine-protein kinase erbB-2 (HER2 ECD4)					Antigen Info
Payload Name	Seco-DUBA					Payload Info
Therapeutic Target	Human deoxyribonucleic acid (hDNA)					Target Info
Linker Name	Mal-PEG2-Val-Cit-PABA-Cyclization Spacer					Linker Info
Conjugate Type	Random Cysteines
Combination Type	duocarmazine
Special Approval(s)	Fast track (FDA)

Bystander Killing Effect	Description	Reference
yes	Next, the ability of SYD985 and T-DM1 to kill HER2-negative bystander tumor cells was explored. NCI-H520 (HER2 0) cells were cocultured (5,000 cells of each cell type per well) with one of the following HER2-positive cell lines, SK-BR-3 (HER2 3+), SK-OV-3 (HER2 2+), or MDA-MB-175-VII (HER2 1+). Cells were treated for 6 days with either SYD985, its nonbinding isotype control ADC, T-DM1, or the active toxin seco-DUBA. NCI-H520 cells were insensitive (IC50 > 50 nmol/L) to SYD985, its isotype control ADC, and T-DM1 but were sensitive for seco-DUBA (IC50 0.04 nmol/L; Fig. 3B and Supplementary Fig. S4D). As shown in Fig. 3B, treatment of SK-BR-3/NCI-H520 and SK-OV-3/NCI-H520 cocultures with 1 ug/mL SYD985 resulted in killing of the HER2 0 NCI-H520 cells, whereas the nonbinding isotype control ADC and T-DM1 did not. Coculturing of cells for 6 days resulted in a dissimilar distribution of the percentage of viable HER2-positive and HER2-negative cells, which was indicated by the results of the isotype control ADC and is most likely due to differences in growth rates.    Click to Show/Hide	[1]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	17	ug/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	54.9	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg AUClast.	[1]
Maximum Observed Concentration (Cmax)	50	ug/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	151	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg AUClast.	[1]
Maximum Observed Concentration (Cmax)	112	ug/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	8080	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	9760	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Maximum Observed Concentration (Cmax)	64.5	ug/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	249	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	261	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Maximum Observed Concentration (Cmax)	75.1	ug/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	441	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	449	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Maximum Observed Concentration (Cmax)	15.2±6/8	ug/mL	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1725±830	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Maximum Observed Concentration (Cmax)	23.3	ug/mL	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1332	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	54.9	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg AUClast.	[1]
Volume of Distribution (Vd)	92.9	mL/kg	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	151	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg AUClast.	[1]
Volume of Distribution (Vd)	201.8	mL/kg	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	8080	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	9760	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Volume of Distribution (Vd)	69.2	mL/kg	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	249	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	261	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Volume of Distribution (Vd)	813	mL/kg	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	441	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	449	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Volume of Distribution (Vd)	334	mL/kg	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	1725±830	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Volume of Distribution (Vd)	54.9±14.3	L/kg	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1332	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]
Volume of Distribution (Vd)	58	L/kg	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	54.9	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	151	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	8080	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	9760	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	249	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	261	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	441	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	449	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Area Under the Concentration-Time Curve (AUC)	1725±830	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1332	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	9.5	h	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	54.9	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg AUClast.	[1]
Clearance (CL)	18.2	mL/h/kg	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 1 mg/kg.	[1]
Elimination Half-Life (t1/2)	55	h	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	151	ug*h/mL	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg AUClast.	[1]
Clearance (CL)	19.7	mL/h/kg	Pharmacokinetic parameters for SYD985 in BT-474-tumor-bearing mice after a single i.v. bolus injection of ADC, 3 mg/kg.	[1]
Elimination Half-Life (t1/2)	96.2	h	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	8080	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	9760	ug*h/mL	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Clearance (CL)	0.51	mL/h/kg	ADC pharmacokinetic parameters in CES1c -/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Elimination Half-Life (t1/2)	87.9	h	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	249	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	261	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Clearance (CL)	19.2	mL/h/kg	ADC pharmacokinetic parameters in CES1c +/+ transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Elimination Half-Life (t1/2)	30.4	h	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985.	[2]
Area Under the Concentration-Time Curve (AUC)	441	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUClast.	[2]
Area Under the Concentration-Time Curve (AUC)	449	ug*h/mL	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of5 mg/kg SYD985, AUCinf.	[2]
Clearance (CL)	11.1	mL/h/kg	ADC pharmacokinetic parameters in CES1c +/- transgenic mice after a single i.v. bolus injection of 5 mg/kg SYD985.	[2]
Elimination Half-Life (t1/2)	52.5±20.3	h	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1725±830	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Clearance (CL)	20.5±12.3	mL/day/kg	Comparison of SYD985 conjugated antibody PK parameters in human, 1.2 mg/kg.	[2]
Elimination Half-Life (t1/2)	63.7	h	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]
Area Under the Concentration-Time Curve (AUC)	1332	ug*h/mL	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]
Clearance (CL)	18	mL/day/kg	Comparison of SYD985 conjugated antibody PK parameters in MAXF1162 tumor bearing CES1c -/- SCID mice, 1.0 mg/kg.	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Progression Free Survival	NCT03262935	PHASE3	A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer    Click to Show/Hide
Progression Free Survival	NCT02277717	PHASE1	A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors    Click to Show/Hide
Objective Response Rate (ORR)	NCT02277717	PHASE1	A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors    Click to Show/Hide
Undisclosed	NCT04983238	PHASE1|||PHASE2	A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985    Click to Show/Hide
Undisclosed	NCT04602117	PHASE1	ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial
Undisclosed	NCT01042379	PHASE2	I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Undisclosed	NCT04205630	PHASE2	A Single-arm Phase II Trial to Evaluate the Safety and Efficacy of the Antibody-Drug Conjugate (ADC) SYD985 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Endometrial Carcinoma Who Previously Progressed on or After First Line Platinum-based Chemotherapy    Click to Show/Hide
Undisclosed	NCT04235101	PHASE1	A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.    Click to Show/Hide
Undisclosed	NCT03262935	Phase 3	A multi-centre, open-label, randomized clinical trial comparing the efficacy and safety of the antibody-drug conjugate SYD985 to physician's choice in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.    Click to Show/Hide
Undisclosed	NCT01042379	Phase 2	I-SPY trial (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2).
Undisclosed	NCT04205630	Phase 2	A single-arm phase 2 trial to evaluate the safety and efficacy of the antibody-drug conjugate (ADC) SYD985 in patients with human epidermal growth factor receptor 2 (HER2)-expressing endometrial carcinoma who previously progressed on or after first line platinum-based chemotherapy.    Click to Show/Hide
Undisclosed	NCT02277717	Phase 1	A two part first-in-human phase 1 study (with expanded cohorts) with the antibody-drug conjugate SYD985 to evaluate the safety, pharmacokinetics and efficacy in patients with locally advanced or metastatic solid tumors.    Click to Show/Hide
Undisclosed	NCT04235101	Phase 1	A two-part phase 1 study with the antibody-drug conjugate SYD985 in combination with niraparib to evaluate safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumors.    Click to Show/Hide
Undisclosed	NCT04602117	Phase 1	ISPY-P1.01: evaluating the safety of weekly paclitaxel with trastuzumab duocarmazine (SYD985) in patients with metastatic cancer: a phase 1/Ib trial.
Undisclosed	NCT04983238	Phase 1	A multicenter, randomized, double-blind, placebo-controlled trial with a single arm run-in period to evaluate the safety and efficacy of sodium thiosulfate (BYON5667) Eye drops to reduce ocular toxicity in cancer patients treated with SYD985.    Click to Show/Hide

Standard Type	Value	Units	Animal Model (No. of PDX)
Tumor Growth Inhibition value (TGI)	≈ 33.3	%	Breast cancer PDX model (PDX: MAXF-1162)
Tumor Growth Inhibition value (TGI)	≈ 42.9	%	Breast cancer PDX model (PDX: MAXF 449)
Tumor Growth Inhibition value (TGI)	≈ 65	%	Breast cancer PDX model (PDX: HBCx-34)
Tumor Growth Inhibition value (TGI)	≈ 66.7	%	Breast cancer PDX model (PDX: ST313)
Tumor Growth Inhibition value (TGI)	≈ 75	%	Gastric cancer PDX model (PDX: GXA3057)
Tumor Growth Inhibition value (TGI)	≈ 90	%	Gastric cancer PDX model (PDX: GXA3038)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Bladder cancer PDX model (PDX: BXF439)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Gastric cancer PDX model (PDX: GXA3054)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Gastric cancer PDX model (PDX: GXA3067)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Breast cancer PDX model (PDX: MAXF-MX1)
Tumor Growth Inhibition value (TGI)	≈ 100	%	Breast cancer PDX model (PDX: HBCx-10)

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Progression Free Survival	7 months
Patients Enrolled	Eligible patients were HER2-positive, unresectable/metastatic breast cancer patients progressing after &ge;2 HER2-targeted therapies (including ado-trastuzumab emtansine), with ECOG &le;2 and adequate organ function. Exclusions included prohibited medication use, hypersensitivity to HER2 agents, active pneumonitis, uncontrolled cardiovascular disease (LVEF <50% or elevated troponin), untreated/symptomatic brain metastases, or prior significant lung conditions. Measurable/evaluable disease per RECIST 1.1 was required.    Click to Show/Hide
Administration Dosage	SYD985, every 3 weeks (Q3W)
Related Clinical Trial
NCT Number	NCT03262935	Clinical Status	PHASE3
Clinical Description	A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer
Primary Endpoint	Efficacy assessments include progression-free survival (PFS) by central review (RECIST v1.1) and death from randomization through 31March2021, overall survival (OS) monitored until 30June2022, and objective response rate (ORR) via complete/partial responses up to 31March2021. Investigator-assessed PFS and patient-reported quality of life (EORTC QLQ-C30) were also tracked through primary analysis.    Click to Show/Hide
Other Endpoint	Key efficacy endpoints comprised central and investigator-evaluated PFS (both per RECIST v1.1) from randomization until progression/death (primary data cutoff: 31March2021), OS until death (final cutoff: 30June2022), and ORR. Quality of life was measured via EORTC QLQ-C30's 0-100 scale, with positive/negative changes indicating improvement/decline in health status.    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Progression Free Survival	9.4 months
Patients Enrolled	Phase I (Part I) enrolls any advanced solid tumor patients refractory to standard therapy, while Phase II (Part II) focuses on HER2-positive breast/gastric/urothelial/endometrial cancers. Key requirements: ECOG &le;1, life expectancy >12 weeks, and adequate organ function. Critical exclusions: recent anthracyclines (<3 months) or cardiotoxicity (LVEF <55% /prior trastuzumab-related declines), active brain metastases, or hypersensitivity to HER2-targeted therapies.    Click to Show/Hide
Administration Dosage	IV (in the vein) infusion every three weeks. Number of Cycles: until cancer progression or unacceptable toxicity develops. Different doses.
Related Clinical Trial
NCT Number	NCT02277717	Clinical Status	PHASE1
Clinical Description	A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors
Primary Endpoint	The primary safety endpoint is incidence of dose-limiting toxicities during the first 21-day cycle, establishing the maximum tolerated dose.
Other Endpoint	Secondary outcomes include long-term safety monitoring (AEs over 2 years), pharmacokinetic profiling (AUC and Cmax of SYD985 at multiple timepoints), hematologic/biochemical changes, immunogenicity (anti-drug antibodies), and antitumor activity (ORR assessed every two cycles).
Experiment 3 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Objective Response Rate (ORR)	33%
Patients Enrolled	Phase I (Part I) enrolls any advanced solid tumor patients refractory to standard therapy, while Phase II (Part II) focuses on HER2-positive breast/gastric/urothelial/endometrial cancers. Key requirements: ECOG &le;1, life expectancy >12 weeks, and adequate organ function. Critical exclusions: recent anthracyclines (<3 months) or cardiotoxicity (LVEF <55% /prior trastuzumab-related declines), active brain metastases, or hypersensitivity to HER2-targeted therapies.    Click to Show/Hide
Administration Dosage	IV (in the vein) infusion every three weeks. Number of Cycles: until cancer progression or unacceptable toxicity develops. Different doses.
Related Clinical Trial
NCT Number	NCT02277717	Clinical Status	PHASE1
Clinical Description	A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors
Primary Endpoint	The primary safety endpoint is incidence of dose-limiting toxicities during the first 21-day cycle, establishing the maximum tolerated dose.
Other Endpoint	Secondary outcomes include long-term safety monitoring (AEs over 2 years), pharmacokinetic profiling (AUC and Cmax of SYD985 at multiple timepoints), hematologic/biochemical changes, immunogenicity (anti-drug antibodies), and antitumor activity (ORR assessed every two cycles).
Experiment 4 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	Eligible patients are &ge;18 with HER2-positive (IHC 1+ for single-arm; IHC 3+/ISH+ for randomized breast cancer cohort) unresectable/metastatic tumors, ECOG &le;1, and adequate organ function. Key exclusions: prohibited medications, trastuzumab hypersensitivity, keratitis, LVEF <50%, pulmonary/cardiovascular diseases, severe systemic illness, or active brain metastases needing steroids/surgery within 8 weeks. Contact lens use is prohibited during treatment.    Click to Show/Hide
Administration Dosage	BYON5667 eye drops should be self-administered daily during waking hours. SYD985, every 3 weeks (Q3W)
Related Clinical Trial
NCT Number	NCT04983238	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985
Primary Endpoint	The primary efficacy endpoint evaluates the percentage of patients experiencing SYD985-related ocular adverse events (Grade ≥1) by Day 63 after using BYON5667 eye drops.
Other Endpoint	Secondary assessments include ocular toxicity severity (Day 63/126), tolerability via questionnaire (0-10 discomfort scale), visual function (NEI VFQ-25), time to first ocular AE, discontinuation rates due to toxicity, and SYD985 efficacy/safety endpoints (ORR, PFS, OS, and treatment-emergent AEs) monitored for up to 2 years.
Experiment 5 Reporting the Activity Date of This ADC					[6]
Patients Enrolled	Eligible patients (&ge;18 years) have HER2-positive/low advanced solid tumors (breast, gastroesophageal, etc.), 1-4 prior therapy lines (dependent on subtype), ECOG 0-2, adequate organ function, and measurable disease (expansion cohort). Exclusions: recent anthracyclines, uncontrolled illness, LVEF <50%, active pneumonitis, corneal disease, CNS metastases, or trastuzumab hypersensitivity. Contraception is mandatory.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT04602117	Clinical Status	PHASE1
Clinical Description	ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial
Primary Endpoint	Safety and tolerability of weekly paclitaxel plus tri-weekly trastuzumab duocarmazine (SYD985) will be assessed via CTCAE v5.0 (up to 12 months), focusing on toxicity rates, DLTs, MTD, and RP2D. Preliminary efficacy (RECIST 1.1) includes CBR and ORR at 6 months.
Other Endpoint	Key efficacy endpoints (RECIST 1.1) are PFS and DOR (up to 12 months) in advanced solid tumor patients treated with paclitaxel-SYD985, alongside safety monitoring of treatment-related AEs.
Experiment 6 Reporting the Activity Date of This ADC					[7]
Patients Enrolled	Eligible patients have untreated, measurable (&ge;2.5 cm), stage II-III or non-metastatic stage IV breast cancer, ECOG 0-1, adequate organ function, and meet specific biomarker criteria (e.g., MammaPrint High or ER-/HER2+). Exclusions: prior chemotherapy/radiation, uncontrolled cardiac/medical conditions, pregnancy, or recent investigational drug use within 30 days. MRI-incompatible implants are prohibited.    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT01042379	Clinical Status	PHASE2
Clinical Description	I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Primary Endpoint	The primary objective is to evaluate if adding experimental agents to standard neoadjuvant chemotherapy improves pathologic complete response (pCR) rates in breast cancer patients, assessed post-surgery after up to 36 weeks of treatment.
Other Endpoint	Secondary goals include developing biomarker-based predictive models for pCR and residual cancer burden (RCB), tracking 3- and 5-year RFS/OS, monitoring treatment-related AEs/SAEs, and assessing tumor dynamics via MRI at four time points (baseline to pre-surgery).
Experiment 7 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Eligible patients are females with HER2-expressing (IHC 1+/2+/3+ or ISH+) recurrent/metastatic endometrial carcinoma, progressed after first-line platinum therapy (&le;1 prior non-cytotoxic systemic therapy allowed). Key exclusions: LVEF <50%, uncontrolled cardiovascular/pulmonary disease, active brain metastases, or prior trastuzumab hypersensitivity. Measurable disease (RECIST 1.1) and ECOG &le;2 are required.    Click to Show/Hide
Administration Dosage	SYD985, Intravenous, every 3 weeks (Q3W)
Related Clinical Trial
NCT Number	NCT04205630	Clinical Status	PHASE2
Clinical Description	A Single-arm Phase II Trial to Evaluate the Safety and Efficacy of the Antibody-Drug Conjugate (ADC) SYD985 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Endometrial Carcinoma Who Previously Progressed on or After First Line Platinum-based Chemotherapy
Primary Endpoint	The primary endpoint evaluates Objective Response Rate (ORR) over 2 years, defined as the proportion of patients achieving complete or partial responses per RECIST v1.1 criteria.The primary endpoint evaluates Objective Response Rate (ORR) over 2 years, defined as the proportion of patients achieving complete or partial responses per RECIST v1.1 criteria.    Click to Show/Hide
Other Endpoint	Key secondary endpoints include Progression-Free Survival (PFS) and Overall Survival (OS) over 2 years, measuring time to progression/death and overall mortality, respectively. Treatment-emergent AEs will be graded via CTCAE v5.0.
Experiment 8 Reporting the Activity Date of This ADC					[9]
Patients Enrolled	Eligible patients (&ge;18 years) must have HER2-positive (IHC 1+) advanced/metastatic breast, ovarian, or endometrial cancer (Part 2) or any solid tumor (Part 1) after failing standard therapy, with measurable disease (RECIST 1.1), ECOG &le;1, and adequate organ function. Key exclusions: prior DUBA-ADCs, recent anthracyclines/anticancer therapies, LVEF <50%, significant cardiovascular/pulmonary disease, active brain metastases, or unresolved treatment-related toxicities (>Grade 1). Tumor biopsy (fresh or archival &le;6 months) is mandatory unless unavailable.    Click to Show/Hide
Administration Dosage	SYD985, Intravenous, every 3 weeks (Q3W) Niraparib taken orally and either 100 mg, 200 mg or 300 mg once daily for either 1, 2 or 3 weeks.
Related Clinical Trial
NCT Number	NCT04235101	Clinical Status	PHASE1
Clinical Description	A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.
Primary Endpoint	The primary objective is to evaluate dose-limiting toxicities during the first treatment cycle (21-day timeframe) to establish the safety and tolerability profile of the SYD985 and niraparib combination regimen.
Other Endpoint	Secondary objectives include safety assessment (AE incidence over 2 years), pharmacokinetic evaluation (AUC and Cmax of SYD985/niraparib up to 6 months), immunogenicity (anti-SYD985 antibodies), hematologic/clinical chemistry changes, and efficacy (ORR assessed every 2 cycles initially, then every 4 cycles).
Experiment 9 Reporting the Activity Date of This ADC					[10]
Related Clinical Trial
NCT Number	NCT03262935	Clinical Status	Phase 3
Clinical Description	A multi-centre, open-label, randomized clinical trial comparing the efficacy and safety of the antibody-drug conjugate SYD985 to physician's choice in patients with HER2-positive unresectable locally advanced or metastatic breast cancer.
Experiment 10 Reporting the Activity Date of This ADC					[11]
Related Clinical Trial
NCT Number	NCT01042379	Clinical Status	Phase 2
Clinical Description	I-SPY trial (investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2).
Experiment 11 Reporting the Activity Date of This ADC					[12]
Related Clinical Trial
NCT Number	NCT04205630	Clinical Status	Phase 2
Clinical Description	A single-arm phase 2 trial to evaluate the safety and efficacy of the antibody-drug conjugate (ADC) SYD985 in patients with human epidermal growth factor receptor 2 (HER2)-expressing endometrial carcinoma who previously progressed on or after first line platinum-based chemotherapy.
Experiment 12 Reporting the Activity Date of This ADC					[13]
Related Clinical Trial
NCT Number	NCT02277717	Clinical Status	Phase 1
Clinical Description	A two part first-in-human phase 1 study (with expanded cohorts) with the antibody-drug conjugate SYD985 to evaluate the safety, pharmacokinetics and efficacy in patients with locally advanced or metastatic solid tumors.
Experiment 13 Reporting the Activity Date of This ADC					[14]
Related Clinical Trial
NCT Number	NCT04235101	Clinical Status	Phase 1
Clinical Description	A two-part phase 1 study with the antibody-drug conjugate SYD985 in combination with niraparib to evaluate safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumors.
Experiment 14 Reporting the Activity Date of This ADC					[15]
Related Clinical Trial
NCT Number	NCT04602117	Clinical Status	Phase 1
Clinical Description	ISPY-P1.01: evaluating the safety of weekly paclitaxel with trastuzumab duocarmazine (SYD985) in patients with metastatic cancer: a phase 1/Ib trial.
Experiment 15 Reporting the Activity Date of This ADC					[16]
Related Clinical Trial
NCT Number	NCT04983238	Clinical Status	Phase 1
Clinical Description	A multicenter, randomized, double-blind, placebo-controlled trial with a single arm run-in period to evaluate the safety and efficacy of sodium thiosulfate (BYON5667) Eye drops to reduce ocular toxicity in cancer patients treated with SYD985.

Experiment 1 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 33.30%	High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: MAXF-1162)
Experiment 2 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 42.90%	Low HER2 expression (HER2+; IHC +; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: MAXF 449)
Experiment 3 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 65%	Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: HBCx-34)
Experiment 4 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 66.70%	Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: ST313)
Experiment 5 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 75%	Low HER2 expression (HER2+; IHC +; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Gastric cancer PDX model (PDX: GXA3057)
Experiment 6 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90%	Moderate HER2 expression (HER2++; IHC 2+; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Gastric cancer PDX model (PDX: GXA3038)
Experiment 7 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Bladder cancer PDX model (PDX: BXF439)
Experiment 8 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	High HER2 expression (HER2+++; IHC 3+; FISH+)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Gastric cancer PDX model (PDX: GXA3054)
Experiment 9 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate HER2 expression (HER2++; IHC 2+; FISH+)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 10 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Gastric cancer PDX model (PDX: GXA3067)
Experiment 10 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Low HER2 expression (HER2+; IHC +; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: MAXF-MX1)
Experiment 11 Reporting the Activity Date of This ADC					[17]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Low HER2 expression (HER2+; IHC +; FISH-)
Method Description	All treatments were conducted at day 0 by a single dose, i.v, 3 mg/kg x1 injection into the tail vein, Data, depicted as mean tumour volume, consists of 6-8 animals per experimental group.
In Vivo Model	Breast cancer PDX model (PDX: HBCx-10)

Ref 1	The Preclinical Profile of the Duocarmycin-Based HER2-Targeting ADC SYD985 Predicts for Clinical Benefit in Low HER2-Expressing Breast Cancers
Ref 2	Unraveling the Interaction between Carboxylesterase 1c and the Antibody-Drug Conjugate SYD985: Improved Translational PK/PD by Using Ces1c Knockout Mice
Ref 3	SYD985 vs. Physician's Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer
Ref 4	First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients
Ref 5	Evaluation of Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985
Ref 6	ISPY-P1.01:Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer
Ref 7	I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
Ref 8	SYD985 in Patients With HER2-expressing Recurrent, Advanced or Metastatic Endometrial Carcinoma
Ref 9	Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors
Ref 10	A Multi-centre, Open-label, Randomized Clinical Trial Comparing the Efficacy and Safety of the Antibody-drug Conjugate SYD985 to Physician's Choice in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer, NCT03262935
Ref 11	I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2), NCT01042379
Ref 12	A Single-arm Phase II Trial to Evaluate the Safety and Efficacy of the Antibody-Drug Conjugate (ADC) SYD985 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Endometrial Carcinoma Who Previously Progressed on or After First Line Platinum-based Chemotherapy, NCT04205630
Ref 13	A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors, NCT02277717
Ref 14	A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors. NCT04235101
Ref 15	ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial, NCT04602117
Ref 16	A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With a Single Arm run-in Period to Evaluate the Safety and Efficacy of Sodium Thiosulfate (BYON5667) Eye Drops to Reduce Ocular Toxicity in Cancer Patients Treated With SYD985, NCT04983238
Ref 17	Anti-integrin immunoconjugates, methods and uses.