Anti-tumor activity and toxicokinetics analysis of MGAH22, an anti-HER2 monoclonal antibody with enhanced Fcγ receptor binding properties

Table 1 Pharmacokinetic parameters for MGAH22 and RES120 in cynomolgus monkeys

Study	Monoclonal antibody	Dose, mg/kg	Sex	C_max, mg/mL	AUC_0-¥, mg-hour/mL	T_1/2b, days	Clearance, mL/hour	V_ss, mL
Single-dose	RES120	50	Male	1.40 ± 0.32	285.7 ± 4.2	11.7 ± 2.4	0.44 ± 0.01	170 ± 36
			Female	1.43 ± 0.05	311.8 ± 54.6	12.0 ± 2.3	0.41 ± 0.07	158 ± 15
	MGAH22	50	Male	1.62 ± 0.10	294.1 ± 53.2	9.3 ± 1.8	0.43 ± 0.07	132 ± 2
			Female	1.70 ± 0.14	314.2 ± 31.3	9.7 ± 1.1	0.40 ± 0.04	127 ± 8
Repeat-dose	MGAH22 (first dose)	15	Male	0.43 ± 0.06	57.0 ± 11.2	5.6 ± 2.0	0.82 ± 0.18	148 ± 35
			Female	0.43 ± 0.40	42.8 ± 9.7	5.1 ± 1.2	1.09 ± 0.24	144 ± 27
		50	Male	1.37 ± 0.23	205.7 ± 127.0	6.9 ± 5.0	0.82 ± 0.28	161 ± 24
			Female	2.85 ± 1.37	286.6 ± 98.2	6.6 ± 4.8	0.57 ± 0.21	109 ± 46
		150	Male	4.10 ± 0.49	558.1 ± 168.6	7.3 ± 3.7	0.78 ± 0.23	176 ± 60
			Female	6.22 ± 1.44	882.9 ± 347.7	7.9 ± 3.6	0.55 ± 0.32	127 ± 34
	MGAH22 (sixth dose)	15	Male	0.89 ± 0.11	229.8 ± 82.1	8.9 ± 4.3	0.24 ± 0.12	66 ± 6
			Female	0.98 ± 0.33	209.4 ± 110.4	8.7 ± 4.6	0.29 ± 0.16	90 ± 51
		50	Male	4.90 ± 5.34	975.5 ± 747.1	8.8 ± 3.0	0.22 ± 0.13	65 ± 34
			Female	7.20 ± 5.70	1,040.4 ± 657.6	7.3 ± 4.7	0.20 ± 0.12	41 ± 18
		150	Male	6.87 ± 1.64	1,330.3 ± 456.7	7.3 ± 3.0	0.36 ± 0.13	81 ± 14
			Female	11.00 ± 4.89	1,963.5 ± 1,273.1	8.8 ± 2.4	0.31 ± 0.19	73 ± 36

Data are presented as mean ± standard deviation. AUC_0-¥, area under the curve from zero to infinity; C_max, maximal serum concentration; MGAH22, chimeric anti-HER2 monoclonal antibody with an optimized Fc domain; RES120, chimeric anti-HER2 monoclonal antibody with wild-type human immunoglobulin G 1 Fc domain; T_1/2β, elimination half-life; V_ss, volume of distribution at steady state.

ISSN: 1465-542X