  The US FDA's Project Optimus initiative that emphasizes dose optimization
prior to marketing approval represents a pivotal shift in oncology drug
development. It has a ripple effect for rethinking what changes may be made to
conventional pivotal trial designs to incorporate a dose optimization
component. Aligned with this initiative, we propose a novel Seamless Phase
II/III Design with Dose Optimization (SDDO framework). The proposed design
starts with dose optimization in a randomized setting, leading to an interim
analysis focused on optimal dose selection, trial continuation decisions, and
sample size re-estimation (SSR). Based on the decision at interim analysis,
patient enrollment continues for both the selected dose arm and control arm,
and the significance of treatment effects will be determined at final analysis.
The SDDO framework offers increased flexibility and cost-efficiency through
sample size adjustment, while stringently controlling the Type I error. This
proposed design also facilitates both Accelerated Approval (AA) and regular
approval in a "one-trial" approach. Extensive simulation studies confirm that
our design reliably identifies the optimal dosage and makes preferable
decisions with a reduced sample size while retaining statistical power.
