Designing "Seamless Phase 1/2" Oncology Trials: Considerations And Best Practices

By Ivan Barrera, MD, Vann Parker, PhD, Meredith Latino, PhD, Vandana Sundaram, Veronica Ruvolo, and Ana Magalhaes

Traditional 3+3 dose escalation is giving way to adaptive designs that reduce patient burden while improving decision accuracy. But seamless Phase 1/2 execution requires cross-functional coordination that most organizations haven't mastered.

Successful seamless designs start with robust pre-study planning and proactive regulatory engagement. Early feedback from FDA or EMA is crucial, particularly when seeking expedited designations. Teams that wait until protocol finalization to engage regulators often find themselves restructuring key elements under time pressure.

Adaptive dose-finding strategies outperform traditional approaches by identifying optimal doses faster and exposing fewer patients to subtherapeutic levels. But execution hinges on cross-functional coordination among operations, data management, biostatistics, and medical oversight that many sponsors underestimate.

Protocol flexibility becomes critical when patient diversity or unexpected safety signals require mid-study adjustments. Clear decision rules and transparent clinical study reporting create the framework for confident go/no-go decisions. Risk-aware project oversight ensures trials stay on track when complexity increases.

Selecting a CRO with deep oncology expertise and proven seamless trial experience is vital for navigating these complexities and delivering transformative therapies faster.