Tumor volume changes of 5 XABCLs after treatment with MDM2is. Mice were treated with vehicle, 45 mg/kg of navtemadlin (Navt), or 25 mg/kg idasanutlin by oral gavage once a day for 5 days per week for 3 weeks or with 0.1 mg/kg of trametinib (Tram) by oral gavage once a day for 4 weeks. Top: tumor volume changes in individual mice bearing 1 of 5 XABCLs as indicated. Middle: waterfall graphs showing tumor volume changes at the end of treatment (day 21). Bottom: adjusted area under curve (AUC) for entire study time period. The values represent the median (line inside box) and the third and first quartile (box) ±1.5× the interquartile range from the top and bottom of the box (error bar). P < .05 for all treatment groups except trametinib when compared with the control. Of note, arrows on the growth curve of TC859 indicate the second cycle of treatment after tumor regrew at 70 to 80 study days. For model TC389, treatment with idasanutlin was also tested. Results showed that both navtemadlin and idasanutlin can significantly inhibit XABCL in vivo.