Statistical considerations
toxicity, death
DISEASE, RECRUITMENT
A Simon two-stage design was used with a target initial response rate of 25% and unacceptable response rate of 10%, two-sided α = 0.02 and 90% power. Stage 1 required recruitment of 37 evaluable patients and at least 5 responses to be observed to continue recruitment to a total of 69 evaluable patients where at least 13 responses were required to infer sufficient activity of the olaparib–ceralasertib combination.ORR, duration of response, and clinical benefit rate were measured in an evaluable population defined as those patients with measurable disease per RECIST at baseline and at least one on-treatment assessment; patients who stopped treatment because of intolerable toxicity or death without having a scan after baseline were evaluable and recorded as nonresponders. Proportions and two-sided 95% confidence intervals (CI) for estimation purposes were reported. For the primary endpoint, in addition to the response rate reported as a percentage (responses/number of evaluable patients), the uniformly minimum-variance unbiased estimator (UMVUE) and adjusted 95% CI are also reported to account for the two-stage design (PFS used the intention-to-treat population. Kaplan–Meier curves were plotted and median PFS was reported with 95% CI. Patients who were alive and progression-free were censored at date of last follow-up; patients who had non-RECIST confirmed progression (e.g., clinical progression only or radiologically confirmed but lesions not measured according to RECIST) were censored at the date progression was reported. The safety population included all patients who had at least one dose of treatment and treatment-emergent AEs where >10% patients reported any grade or any patients reporting grade ≥3 were presented.Analyses used a database snapshot taken on June 15, 2021. Where reported, 