Fig 2. RMC-7977 exhibits anti-tumor activity in xenograft and allograft models of PDAC.

(a-e) Human PDAC xenograft models implanted either subcutaneously (SC) or orthotopically (Ortho) into immunodeficient mice. Tumor-bearing mice were treated with Vehicle or RMC-7977 (10 mg/kg, po, q.d.; n=3–10) for 21–28 days. (a) Boxplot showing percent change in tumor volumes at endpoint compared with baseline at Day 0 in Vehicle and RMC-7977 treatment arms. Each symbol represents one mouse. Source and format of each cell line, KRAS mutation, and tumor locations are indicated in the graph. Study arms were compared by Student’s unpaired t-test (*, p<0.05; **, p<0.01; ****, p<0.0001). (b) Representative bioluminescence images showing signal in HPAF-II orthotropic xenograft tumors at Day 0 and at Day 21 for Vehicle and RMC-7977 treatment arms. (c,d) Representative tumor growth curves for HPAF-II (c) orthotopic and (d) subcutaneous xenograft models treated with Vehicle or RMC-7977 (n=8/group), shown as percent tumor volume change from baseline over the course of treatment. Vehicle and RMC-7977 groups were compared by 2-way repeated measures ANOVA on the last measurement day of the vehicle group (*, p<0.05; ****p<0.0001). Error bars indicate ± s.e.m. (e) Tolerability of RMC-7977 as assessed by percent animal body weight change from baseline over the course of treatment. Error bars indicate ± s.e.m. (f, g) KPCY-derived PDAC cell line (6499c4) was transplanted either subcutaneously or orthotopically into syngeneic mice. Tumor-bearing mice were treated with Vehicle or RMC-7977 (10 mg/kg, po, q.d.; n=9–10/group). (f) Boxplot showing changes in subcutaneous and orthotopic tumor volumes at Day 14, compared with baseline at Day 0, in Vehicle and RMC-7977 treatment arms. Groups compared by Student’s unpaired t-test (***, p<0.001; ****, p<0.0001). Tumor locations as indicated in the graph. (g) Representative IHC images of Vehicle and RMC-7977-treated KPCY allograft tumors stained for phospho-ERK^T202/204 and CC3. Scale bars = 100 μm.