Table III.

Predicted Human Parameters Used in Simulations

	Parameter	Definition	Unit	Value (CV%)	Source
Binding	konCD3, koffCD3, Kd_CD3	Binding of PF-06671008 to CD3	1/nM/h, 1/h nM	1.72, 19.66, 11.4	(7)
	konPcad, koffPcad, Kd_Pcad	Binding of PF-06671008 to P-cadherin		1.57, 0.74, 0.47
Central/peripheral compartment	V 1	Volume of distribution in central compartment	mL/kg	40.2	Allometrically scaled from cynomolgus monkey PK analysis (16) kel = CL/V1 k12 = CLd/V1 k21 = Cld/V2
	V 2	Volume of distribution in peripheral compartment	mL/kg	211
	CL	Clearance	mL/h/kg	4.61
	CL D	Inter-compartmental clearance	mL/h/kg	25.2
	sPcad	sPcadherin concentration in central compartment	nM	1.1 (0.4–4.1)	Measured in-house (= 92.7 ng/mL) Median value of healthy subjects and patient data
	k deg	sPcad degradation rate	1/h	0.15	Allometrically scaled from cynomolgus monkey PK analysis (0.31 1/h in cyno) (16)
	k degcx	sPcad-PF-06671008 complex degradation rate	1/h	0.115	Assumed to equal PF-06671008 elimination rate (CL/V1)
	Tcells p	T cell concentration in central compartment	Cells/μL	5000	(23)
	CD3	CD3 expression on T cells	Receptors/cell	100,000	(17,18)
Tumor disposition of PF-06671008/T cells	P	Permeability of drug into tumor	μm/d	334	(19)
	D	Diffusivity of drug into tumor	cm2/d	0.022
	ε	Void fraction in tumor for drug	–	0.24
	Rcap	Capillary radius	μm	8
	Rkrogh	Average distance between 2 capillaries	μm	75
	Tcells t a	Number of T cells in tumor	Cells/g of tumor	6.49e5	(24)
	Tumor cellst	Number of Tumor cells	Cells/g of tumor	1e8	(21)
	mPcad	P-cadherin expression on tumor cells	Receptors/cell	28,706	(15)
	Rtumor	Tumor radius	cm	1	Assumed
	k int	Internalization rate with PBMCs	Day−1	0.1728 (−)	Estimated from mouse tumor PK data. Represents 96 h half-life of internalization.

^aAssume no proliferation in tumor; ksyn = kdeg*sPcad. MWt of PF-06671008 = 105 kDa, MWt of sPcad = 85 kDa