Figure 2. Axl inhibition in mice with advanced PDA improves survival.

KIC mice (A) and Pan02 tumor-bearing mice (B) were enrolled in a survival study and randomized to vehicle (0.5% [w/w] hydroxypropyl methylcellulose/0.1% [w/w] Tween 80 in water, control, PO BID), BGB324 (50 mg/kg PO BID), gemcitabine (25 mg/kg IP twice a week), and gemcitabine + BGB324. Therapy was initiated at day 49 (KIC) or day 17 post tumor cell injection (Pan02) and maintained until sacrifice. C) In vivo assessment of treatment response of subcutaneously (SC) implanted pancreatic PDX. Panc 281 and Panc 163 were implanted SC on the flanks of athymic mice (n = 8–10/group). When tumors were established, mice were treated with vehicle (control, PO BID), BGB324 (50 mg/kg PO BID), gemcitabine (25 mg/kg IP twice a week), or the combination. Effects on tumor growth are shown after 4 weeks of treatment. D) Panc 265 was orthotopically implanted into nu/nu athymic mice. After tumor establishment, mice were treated as in (C) (n = 6–7/group). Total gross metastasis was determined by evaluation of liver, diaphragm, GI lymph nodes, and lung at the time of sacrifice. BGB324 alone or in combination with gemcitabine significantly reduced the rate of metastasis (p=0.001 vs control, Fisher’s exact test)