Want to enter phase 2 with an optimal dose and a clear predictive biomarker? Then set your phase 1 biomarker strategy up for success!

Here's an underutilized approach that's transforming how smart teams navigate dose escalation:

**Strategic backfill at promising dose levels.**

Instead of the traditional "3+3, move up, done" approach, consider expanding cohorts at doses showing early activity.

This allows you to:
• Strengthen pharmacodynamic signals in active doses before Phase 2
• Build confidence in your predictive biomarker hypothesis with appropriately powered analysis
• Generate robust dose-response data (hello, Project Optimus)
• Identify the optimal biological dose, not just the MTD

One client used this approach using molecular and clinical response as a gating strategy to initiate backfill. We backfilled with 6 additional patients at each level after that gate with stratified biomarker positive patients.

Result? An improved ORR and clear biomarker-response relationships that informed both dose selection AND patient selection for Phase 2.

Yes, it requires more patients upfront. But it beats redesigning your Phase 2 when initial biomarker data looks promising but underpowered.

The key: Plan this flexibility into your protocol from day one. Most amendments happen because teams didn't anticipate what they'd want to do with encouraging early signals (or lack of them).

Is your Phase 1 designed to generate actionable biomarker insights—or just check regulatory boxes?