Aims: Adavosertib, a WEE1 inhibitor, has been studied for safety and efficacy as monotherapy and in combination therapy. The phase 2b ADAGIO trial evaluated adavosertib monotherapy for uterine serous carcinoma with a recommended dose of 300 mg dosing on days 1 to 5 and days 8 to 12 of 21‑day cycle. However, reports of severe neutropaenia and dose reduction in approximately half of patients at 300 mg suggested potential tolerability concerns. Methods: We conducted a model-based benefit-risk analysis, including an exposure-safety analysis, pooling data from all AstraZeneca-sponsored monotherapy studies. The analysis focused on the relationship between adavosertib exposure and incidence of adverse events such as haematological and gastrointestinal toxicities. A preliminary exposure-efficacy analysis was conducted based on available efficacy data from the ADAGIO study. Results: A strong correlation is observed between adavosertib exposure and predicted probability of developing neutropenia. Also, baseline creatinine clearance (bCLCr) was identified as an independent factor for severe neutropaenia development. Patients with bCLCr ≥50 mL/min were less likely to experience severe neutropaenia than those with bCLCr <50 ml/min. The model shows that a dose reduction from 300 to 250 mg reduces the predicted probability of neutropaenia by 55% when compared at the 95th percentile exposure range at these doses. Contrary to exposure safety, exposure-efficacy relationship was similar across doses. Conclusion: The model-based approach identifies risk factors, aiding in the decision to use a 250 mg monotherapy dose. This regimen may manage hematological toxicities across studies. Reducing adavosertib doses minimizes risks, underscoring the need for dose adjustment