Table 1.

Therapeutic effect of H-Zt/g4-MMAE in comparison with H-Zt/g4-DM1 in inhibition of xenograft tumors derived from human pancreatic and colorectal cancer cells^a

Anti-RON ADCs Evaluated	Tumor growth inhibition based on average tumor weights (gram)
	Colorectal Cancer				Pancreatic cancer
	LoVo	HCT116	HT29	SW620	Pan-1	BxPc-3	FG	L3.6pl
M-Zt/g4-DM1	ND	D16/D16:6.23/156 (96.02%)	D16/D16:5.92/180 (96.67%)	D16/D16:110/624 (82.37%)	ND	D32/D32: 0.06/0.7 (91.8%)	D20/D32: 1.89/2.49 (24.1%)	D16/D28: 1.41/2.54 (44.6%)
H-Zt/g4-DM1	D36/D36: 1.11/1.0 (9.01%)	D36/D36: 0.32/1.88 (82.98%)	D32/D36: 0.21/1.71 (87.72%)	D36/D36: 0.14/1.95 (92.82%)	D32/D32 1.25/1/32 (−5.30%)	D32/D32 0.08/0.81 (90.12%)	D32/d32 1.67/2.33 (28.33%)	D32/D32 1.31/2.44 (46.31%)
M-Zt/g4-MMAE	ND	ND	ND	ND	D44/44: 0.44/0,41 (−7.32)	D44/D52: 0.01/1.19 (99.2%)	D24/D44: 0.03/1.54 (98.1)	D24/D44: 0.02/1.58 (98.7)
H-Zt/g4-MMAE	D44/D44: 1.33/1.56 (14.7%)	D36/D52: 0.01/2.12 (99.5%)	D32/D52: 0.01/1.76 (99.4%)	D36/D52: 0.02/1.63 (98.8%)	D44/D44: 1.29/1.3 (3.70%)	D40/D52: 0.01/1.97 (99.9%)	D28/D52: 0.01/1.62 (99.4%)	D28/D52: 0.01/2.0 (99.5%)

^aAnti-RON ADCs including mouse (M)-Zt/g4-DM1, H-Zt/g4-DM1, M-Zt/g4-MMAE, and H-Zt/g4-MMAE were prepared according to methods detailed in a previous report [31] and in Experimental Procedures. The drug to antibody ratios for each ADC are 3.72:1 for M-Zt/g4-DM1, 3.83:1 for H-Zt/g4-DM1, 3.67:1 for M-Zt/g4-MMAE, and 3.77:1 for H-Zt/g4-MMAE, respectively. CRC and PDAC xenografts in mouse model were established as detailed in Experimental Procedures. Individual ADCs were used at 20 mg/kg in the Q12 × 2 schedules. At the end of the study dependent on growth rate of individual models, tumors were collected and weighted to reach an average value for each group. The percentages of inhibition for tumor growth were calculated as detailed in Experimental Procedures

The percentages of inhibition were highlighted in bold