Extended Data Fig. 5: Body weight changes in mice treated with MTX-531 alone or in combination.
a, Selection of a combination dosage of erlotinib and alpelisib. Mice were treated with the combination of erlotinib and alpelisib daily via oral gavage for 5 weeks (n = 8 mice/group). The daily dose of erlotinib was held constant at 50 mg/kg and the dose of alpelisib was varied (12.5, 25 and 50 mg/kg). Body weight loss of ≥ 20% and/or ≥ 10% treatment-related deaths in a group are considered unacceptable toxicity parameters. Three deaths occurred in each of the two highest dose combination groups. b, Body weight of subcutaneous HNSCC PDX-bearing mice in response to daily oral treatment with MTX-531 at 100 mg/kg. Body weight was monitored throughout the efficacy study shown in Fig. 3b. c, Response of PIK3CA mutant HNSCC NCI 848979-319-R PDX xenografts to daily oral dosing of 150 mg/kg MTX-531. Data are presented as mean values ± SEM. Dosing occurred until individual tumors reached 1000 mm3 to facilitate comparative survival analysis (n = 5 mice/group). A comparison of survival curves was performed using the Log-rank (Mantel-Cox) test (** = p-value ≤ 0.01, *** = p-value ≤ 0.001). d, Body weight of mice bearing CRC PDX models CN0375-F725 (5 mice/group) and UM-CRC 14-929 (5 mice/group) in response to daily treatment with MTX-531 (100 mg/kg PO) in combination with trametinib (1 mg/kg PO). Data are presented as mean values ± SEM. e, Body weight of mice bearing CRC B8324 patient-derived xenografts (5 mice/group) in response to daily oral treatment with MTX-531 (100 mg/kg) in combination with sotorasib (100 mg/kg). Data are presented as mean values ± SEM. For all panels, body weights were recorded 2-3 times per week.
