  2-in-1 design (Chen et al. 2018) is becoming popular in oncology drug
development, with the flexibility of using different endpoints at different
decision time. Based on the observed interim data, sponsors choose either to
seamlessly advance a small phase 2 trial to a full-scale confirmatory phase 3
trial with a pre-determined maximum sample size, or to remain in a phase 2
trial. This approach may increase efficiency in drug development but is rigid
and requires a pre-specified fixed sample size. In this paper, we propose a
flexible 2-in-1 design with sample size adaptation, while retains the advantage
of allowing intermediate endpoint for interim decision. The proposed design
reflects the needs of recent FDA's Project FrontRunner initiative to encourage
using an earlier surrogate endpoint to potentially support accelerated approval
with conversion to standard approval with long term endpoint from the same
randomized study. Additionally, we identify the interim decision cut-off to
allow conventional test procedure at the final analysis. Extensive simulation
studies showed the proposed design require much smaller sample size and shorter
timeline than the simple 2-in-1 design, while achieving similar power. A case
study in multiple myeloma is used to demonstrate the benefits of the proposed
design.
