Improving phase 2/3 trials with an enhanced 2-in-1 adaptive design

Area of Science:

• Clinical Trial Design
• Pharmaceutical Development
• Biostatistics

Background:

• Seamless Phase 2/3 designs accelerate drug development.
• The 2-in-1 adaptive design allows seamless expansion from Phase 2 to Phase 3 using surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS).

Purpose of the Study:

• To enhance the 2-in-1 adaptive design by incorporating a group sequential approach in Phase 3 and an interim analysis in Phase 2 based on the primary endpoint.
• To improve the probability of success and address competitive challenges in oncology drug development.

Main Methods:

• The enhanced 2-in-1 design was applied to an oncology trial.
• The Type I error rate control was mathematically proven.
• Operating characteristics were evaluated through simulation.

Main Results:

• The enhanced design controls the Type I error rate.
• Simulation results indicate that the correlation between surrogate and primary endpoints does not affect the overall success probability.
• The enhanced design increases the probability of success compared to the original 2-in-1 design under the null scenario, without extending study duration.

Conclusions:

• The enhanced 2-in-1 adaptive design offers a robust approach to accelerate oncology drug development.
• This design improves the probability of success while maintaining statistical integrity.
• The findings support the use of enhanced adaptive designs in overcoming drug development challenges.