Statistical analysis
toxicity
The response rate was defined as the proportion of responders among response evaluable patients. Per the Rule of Three, if there are no responders in a sample with Given this combination had not previously been tested in patients with relapsed and refractory EWS, safety stopping rules were used. Two toxicity monitoring rules were used in the trial: one from the original version of the protocol, and another in a protocol amendment required when the original stopping rule was triggered. In the original rule, toxicity was monitored using a Simon's two‐stage design, which required stopping if two or more patients out of nine treated, or three or more patients out of 15 treated, had a cycle 1 DLT. The operating characteristics of this rule were: a null hypothesis that the cycle 1 DLT rate is >30% versus the alternative that the cycle 1 DLT is ≤5%, an expected sample size of 10, a probability of early termination of 0.804 under the null hypothesis, power of 92%, and type 1 error of 9.5%. The revised stopping rule (applied to subsequent patients treated at a lower dose level) was an exact one‐stage rule which required stopping if three or more patients out of 12 treated had a cycle 1 DLT. The operating characteristics of this rule were: a null hypothesis that the cycle 1 DLT rate is ≥39% versus the alternative that the cycle 1 DLT is ≤9%, power of 91.3%, and type 1 error of 9.5%.Analyses of demographic, clinical, safety, and ctDNA data were summarized descriptively. Paired 