Table 1.

Parameter estimates for cytokine PK/PD model using blinatumomab human data and P‐cadherin LP DART cynomolgus monkey data

Parameter	Description	Unit	Estimate (%CV)
			Blinatumomab (human)	P‐cadherin LP DART (monkey)
Emax	Maximum cytokine release rate	pg/mL/hour	3.59 × 103 (14)	2.10 × 105 (72)
EC50	Exposure of active drug species to achieve half‐maximum cytokine release rate	(ng/mL) × (cell/μL)a or ng/mLb	1.00 × 104 (FIXED)	3.00 × 103 (FIXED)
H	Hill coefficient for cytokine release	N/A	9.20 × 10−1 (3)	1.08 × 100 (6)
Imax	Maximum inhibition of cytokine release	N/A	1 (FIXED)	1 (FIXED)
IC50	Cytokine exposure to achieve half‐maximum cytokine inhibition	pg/mL × hour	1.82 × 102 (12)	1.76 × 101 (107)
k deg	Degradation rate for cytokine	hour−1	1.80 × 10−1 (13)	2.5 × 10−1 (16)
K	Priming factor for cytokine release upon 2nd dose	N/A	2.83 × 100 (36)	7.31 × 100 (92)
k kill	Killing rate for tumor cells	hour−1	4.80 × 10−3 (FIXED)c	N/A
BL	Cytokine level at baseline	pg/mL	N/A	1.66 × 101 (31)
MTT	Lag time for cytokine elevation in circulation	hour	N/A	3.21 × 100 (26)
Res prop err	Proportional error	N/A	3.10 × 10−1 (5)	3.20 × 10−1 (5)

%CV, percentage of coefficient of variation; N/A, not applicable; PD, pharmacodynamic; PK, pharmacokinetic; Res Prop Err, residual proportional error.

^aFor T‐cell–engaging bispecific antibody (T‐BsAb) with hematological tumor indication (e.g., blinatumomab). ^bFor T‐BsAb with solid tumor indication (e.g., P‐cadherin LP DART). ^cFIXED: fixed parameter; estimated separately and then fixed in the cytokine model.