Fig. 4

Synergistic prolongation of survival by irradiation and tepotinib-mediated MET inhibition in the SMA-560 glioma model in vivo. A,B. Syngeneic mice were intracranially implanted with SMA-560 glioma cells and treated daily with 100 mg/kg tepotinib from day 6 on or solvent, or with a single dose of 12 Gy on day 7, or in combination. A. Tumor lysates pooled from 2 pre-randomized animals per group were analysed by immunoblot for target inhibition (p-MET) (LH, left hemisphere; RH, right hemisphere without tumor; T, tumor removed from the right hemisphere). B. Kaplan–Meier survival curve (⁺ p < 0.05, ⁺⁺ p < 0.01, versus control; ^## p < 0.01, versus irradiation). C,D. Syngeneic mice were intracranially implanted with GL-261 glioma cells and treated daily with 100 mg/kg tepotinib from day 6 on or solvent, or with a single dose of 10 Gy on day 7, or the combination of both. C. Kaplan–Meier survival curves were analyzed via log-rank test (⁺⁺ p < 0.01, versus control; ^## p < 0.01, versus irradiation). D. Mice surviving in (C) were re-challenged after 13 weeks after initial tumor cell injection with GL-261 cell implantation into the contralateral hemisphere. Naïve mice implanted with GL-261 cells were used as controls. Kaplan–Meier survival curves are shown