Safety
nausea, pneumonia, death, DLTs, fatigue, diarrhea, febrile neutropenia, neutropenia, thrombocytopenia, myalgia, abdominal pain, anemia, dehydration, sepsis, alopecia, all-grade
DISEASE PROGRESSION, PNEUMONIA, NEUTROPENIA, FEBRILE NEUTROPENIA, THROMBOCYTOPENIA, ANEMIA, DEHYDRATION, SEPSIS, ALOPECIA
In total, 60 (96.8%) patients experienced at least one AE. The most commonly occurring all-grade AEs (in ≥ 30% of patients) were diarrhea in 32 (51.6%) patients, nausea and fatigue in 29 (46.8%) patients each, and dehydration in 23 (37.1%) patients. An overview of all-grade AEs occurring in ≥ 10% of patients per dosing schedule is provided in Supplementary Table S1.Fifty-six (90.3%) patients experienced at least one AE related to adavosertib treatment (Supplementary Table S2). Of these, the three most commonly occurring AEs were diarrhea in 31 (50.0%), nausea in 26 (41.9%), and fatigue in 24 (38.7%) patients. Grade ≥ 3 AEs were experienced by 39 (62.9%) patients, of whom 24 (38.7%) had at least one treatment-related grade ≥ 3 AE (Table 
AEs with severity grade ≥ 3 and DLTsDiarrhea (G3); nausea (G2); dehydration (G3)The MTDs are indicated with italics and the RP2D indicated with bold. Fifty serious AEs (SAEs) were reported in 25 (40.3%) patients. Of these, seven (11.3%) patients had 10 treatment-related SAEs: pneumonia n = 2 [3.2%], dehydration n = 2 [3.2%], anemia n = 1 [1.6%], febrile neutropenia n = 1 [1.6%], and thrombocytopenia n = 1 [1.6%]. The death of one patient in cohort qd 3.3 was attributed by the investigator to both disease progression and an SAE of treatment-unrelated grade 5 sepsis.Overall, 12 DLTs were reported in 8 (13.3%) patients (Table AEs led to dose reductions in 17 (27.4%) patients. The most commonly occurring AEs leading to dose reductions (in ≥ 5% of patients) were thrombocytopenia in 5 (8.1%) patients and neutropenia in 4 (6.5%) patients. AEs led to dose interruptions in 25 (40.3%) patients. The most common AEs leading to interruptions in ≥ 5% of patients were diarrhea, fatigue, thrombocytopenia and dehydration, which occurred in 4 (6.5%) patients each. Overall, 4 (6.5%) patients from different cohorts discontinued treatment because of the following AEs: grade 1 alopecia (qd 1.2); grade 2 fatigue and myalgia (qd 2.3); grade 4 thrombocytopenia (qd 3.1); and grade 2 abdominal pain, diarrhea and nausea (qd 3.3).