# Factorial dose finding for drug combinations instead of full dose of everything

Source: https://onco.cc/ideas/idea-tr1-factorial-dose-finding-for-combinations/  
OnCo record `idea-tr1-factorial-dose-finding-for-combinations` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

When two cancer drugs are combined, each is usually given at its full single-agent dose, which often proves too toxic. Testing a grid of dose pairs would find combinations that work with tolerable side effects.

## Summary

Combination phase 1/2 studies use model-based two-agent dose-finding (partial-order CRM, BOIN-COMB) or factorial randomised designs to explore dose pairs, with efficacy and tolerability read-outs at each pair, rather than fixing one agent at its label dose and escalating the other. Regulators expect a justification for each agent's dose in combination labels.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Combination programmes using two-dimensional dose finding will select regimens with lower total dose intensity and substantially lower discontinuation than full-dose combinations, with equal or better efficacy.
- Rationale: Many combination failures (and several withdrawals) were driven by intolerability at full doses of each component; synergy, where present, implies that less of each is needed.
- Proposed test: Apply two-dimensional dose finding to three new combination programmes and compare discontinuation and efficacy in subsequent trials with combinations developed conventionally.
- Maturity: speculative
- Actor: industry

## Sources

- Bottleneck evidence (Wrong doses): FDA Oncology Center of Excellence, Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus

## Connected records

- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- bottlenecks: [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)

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