ADC Name	PF-06804103
Synonyms	PF-06804103    Click to Show/Hide
Organization	Pfizer (Top20 MNC) (Originator)
Drug Status	Phase 1 (discontinued)
Drug-to-Antibody Ratio	4
Structure
	3D MOL			2D MOL
Antibody Name	Trastuzumab-(κK183C+K290C)					Antibody Info
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (HER2)					Antigen Info
Payload Name	Auristatin 0101 (Aur0101)					Payload Info
Payload Target	Microtubule (MT)					Target Info
Linker Name	Mc-Val-Cit-PABC					Linker Info
Conjugate Type	Reactive Cysteines
Combination Type	pelidotin

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	296	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	288	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	2.61	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	1.08	h	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	969	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	965	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	12.6	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	3.6	h	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	2540	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	2500	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	22	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	1.1	h	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	5120	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	5026	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	36.97	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	3.91	h	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	9498	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	8263	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	71.24	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	3.82	h	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	12940	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	12290	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	78.91	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	3.67	h	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	16550	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1, AUCinf.	[1]
Area Under the Concentration-Time Curve (AUC)	15480	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1, AUClast.	[1]
Maximum Observed Concentration (Cmax)	103.1	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1.	[1]
Time to Maximum Concentration (Tmax)	2.42	h	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1.	[1]
Area Under the Concentration-Time Curve (AUC)	966	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	980	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	10.3	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	1	h	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4.	[1]
Area Under the Concentration-Time Curve (AUC)	2790	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	2800	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	29.3	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	1.02	h	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4.	[1]
Area Under the Concentration-Time Curve (AUC)	2970	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	4950	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	43	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	2.43	h	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4.	[1]
Area Under the Concentration-Time Curve (AUC)	7432	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	7504	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	53.29	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	1.1	h	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4.	[1]
Area Under the Concentration-Time Curve (AUC)	10990	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	10730	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	76.52	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	3.81	h	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4.	[1]
Area Under the Concentration-Time Curve (AUC)	11740	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	11990	ug·h/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4, AUCtau.	[1]
Maximum Observed Concentration (Cmax)	82.13	ug/mL	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4.	[1]
Time to Maximum Concentration (Tmax)	4	h	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4.	[1]

Standard Type	Value	Units	Description	Reference
Volume of Distribution (Vd)	5.93	L	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	4.43	L	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	4.74	L	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	2.462	L	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	2.807	L	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	3.165	L	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	3.281	L	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1.	[1]
Volume of Distribution (Vd)	3.93	L	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	4.82	L	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	2.77	L	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	3.037	L	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	3.106	L	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	3.467	L	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4.	[1]
Volume of Distribution (Vd)	61	mL/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103, Mouse.	[2]
Volume of Distribution (Vd)	38.1	mL/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103, Cynomolgus monkey.	[2]
Volume of Distribution (Vd)	38.1	mL/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103 in the clinic and predicted clinical PK of PF-06804103 following IV infusion of 1 h	[2]

Standard Type	Value	Units	Description	Reference
Clearance (CL)	0.0405	L/h	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	4.21	day	Part 1A, PK parameters for PF-06804103 ADC, 0.15 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.0611	L/h	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	2.09	day	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.0373	L/h	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	3.67	day	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.02073	L/h	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	3.495	day	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.0197	L/h	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	4.257	day	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.01884	L/h	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	5.001	day	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.01975	L/h	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1.	[1]
Elimination Half-Life (t1/2)	4.962	day	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 1.	[1]
Clearance (CL)	0.0449	L/h	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	2.34	day	Part 1A, PK parameters for PF-06804103 ADC, 0.5 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	0.0391	L/h	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	3.46	day	Part 1A, PK parameters for PF-06804103 ADC, 1.2 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	0.0217	L/h	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	3.42	day	Part 1A, PK parameters for PF-06804103 ADC, 2.0 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	0.02069	L/h	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	4.177	day	Part 1A, PK parameters for PF-06804103 ADC, 3.0 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	0.01731	L/h	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	5.185	day	Part 1A, PK parameters for PF-06804103 ADC, 4.0 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	0.01971	L/h	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4.	[1]
Elimination Half-Life (t1/2)	5.278	day	Part 1A, PK parameters for PF-06804103 ADC, 5.0 mg/kg, Q3W, cycle 4.	[1]
Clearance (CL)	22.8	mL/day/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103, Mouse.	[2]
Clearance (CL)	7.2	mL/day/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103, Cynomolgus monkey.	[2]
Clearance (CL)	5.52	mL/day/kg	Use of translational modeling and simulation for quantitative comparison of PF-06804103 in the clinic and predicted clinical PK of PF-06804103 following IV infusion of 1 h.	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT03284723	PHASE1	A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	100	%	BT474-M1 cells	Invasive breast carcinoma
Tumor Growth Inhibition value (TGI)	100	%	NCI-N87 cells	Gastric tubular adenocarcinoma

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Objective Response Rate (ORR)	52.40%
Patients Enrolled	Inclusion criteria cover HER2+/- breast/gastric cancer (Part 1A/B, Part 2A/B) resistant to standard therapy, with PS 0-1 and adequate organ function. Exclusions include CNS metastases, anthracycline overdose, Grade 3+ antibody hypersensitivity, active infections, LVEF <50%, or interstitial lung disease. Eligibility is tailored by study part, emphasizing safety and biomarker relevance.    Click to Show/Hide
Administration Dosage	This multi-center, open-label, first-in-patient, phase I study (NCT03284723) has two parts: dose escalation (Part 1) and dose expansion (Part 2). In Part 1, groups of adult patients (pts) with HER2+ BC or HER2+ GC, who are resistant or intolerant to standard therapy or for which no standard therapy is available, received PF-06804103 intravenously once every 21 days (Q3W); dosage was escalated per cohort. Primary objectives were to evaluate the safety and tolerability of PF-06804103, characterize its dose-limiting toxicities (DLTs), and determine the recommended phase 2 dose.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT03284723	Clinical Status	PHASE1
Clinical Description	A Phase 1 Dose Escalation Study Evaluating the Safety and Tolerability of PF-06804103 in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) Positive and Negative Solid Tumors
Primary Endpoint	This section outlines Dose-Limiting Toxicities (DLTs) observed in Part 1A (21-day cycle) and Part 1B (28-day cycle) during the first treatment cycle, categorizing them into hematologic (Grade 4 neutropenia >7 days, febrile neutropenia, thrombocytopenia with bleeding) and non-hematologic (Grade ≥3 toxicities, treatment delays, liver abnormalities). It also details Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), including definitions and timeframes (up to 89.3 weeks for Part 1A, 53.7 weeks for Part 1B). Laboratory abnormalities (hematology, chemistry, urinalysis) and vital sign criteria are summarized, along with response metrics (Objective Response, Duration of Response, PFS, TTP) in Part 2, all assessed per RECIST v1.1.    Click to Show/Hide
Other Endpoint	This segment focuses on clinical outcomes in Part 1 (Objective Response, DR, PFS, TTP) with assessment intervals every 6 (Part 1A) or 8 weeks (Part 1B). Immunogenicity (anti-drug antibodies) and HER2 tumor analysis are included. Pharmacokinetic parameters (Cmax, t1/2, AUCinf, AUCtau, CL, Vss, Rac) for PF-06804103 ADC, total antibody, and unconjugated payload (PF-06380101) are detailed, with data from Part 1A/B (sparse sampling excluded Part 2A). Key metrics like terminal half-life, clearance, and volume of distribution are calculated per dosing intervals (504h for Part 1A, 336h for Part 1B).    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Tumor Growth Inhibition value (TGI)	100%	Moderate HER2 expression (HER2++)
Method Description	In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 10 x106 BT474 cells, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm3. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).    Click to Show/Hide
In Vitro Model	Invasive breast carcinoma	BT474-M1 cells		CVCL_0179
Experiment 2 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Tumor Growth Inhibition value (TGI)	100%	High HER2 expression (HER2+++)
Method Description	In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 1 x106 NCI-N87, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm3. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Ref 1	Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients with HER2-Expressing Solid Tumors: A Phase 1 Dose-Escalation Study
Ref 2	Use of translational modeling and simulation for quantitative comparison of PF-06804103, a new generation HER2 ADC, with Trastuzumab-DM1
Ref 3	PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors
Ref 4	PF-06804103, A Site-specific Anti-HER2 Antibody-Drug Conjugate for the Treatment of HER2-expressing Breast, Gastric, and Lung Cancers. Mol Cancer Ther. 2020 Oct;19(10):2068-2078.