{"entity":{"id":"idea-tr2-qsp-combo-dosing","kind":"idea","name":"Mechanistic computer models to pick combination doses before dosing patients","aka":[],"tldr":"Simulate how two drugs interact in the body and the tumour to pick a starting dose and schedule, instead of guessing from single-drug data.","summary":"Quantitative systems pharmacology models integrate pharmacokinetics, target engagement and downstream biology to predict combination effects and toxicities. FDA's model-informed drug development pathway accepts such models for dose justification. Making a QSP-based schedule proposal a standard component of combination investigational new drug applications would reduce empirical dose-escalation in combinations.","asOf":"2026-09-08","links":[{"label":"FDA model-informed drug development programme","url":"https://www.fda.gov/drugs/development-resources/model-informed-drug-development-paired-meeting-program"}],"tags":[],"related":["idea-tr2-combo-dose-matrix"],"cancers":[],"sections":[],"technologies":["ai-drug-design"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-combination-space","b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Combination trials whose dose and schedule were selected with a pre-specified QSP model will require fewer dose-escalation cohorts and reach recommended phase 2 dose with fewer dose-limiting toxicities than trials using conventional escalation.","rationale":"QSP models predicted the therapeutic window of several bispecifics and ADCs; overlapping toxicity in combinations is largely predictable from pharmacology.","test":"Retrospectively apply QSP dose selection to ten completed combination phase 1 trials and compare predicted with observed recommended doses; then run prospectively in five new trials.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":3},"route":"/ideas/idea-tr2-qsp-combo-dosing/","neighbours":{"idea":[{"id":"idea-tr2-combo-dose-matrix","kind":"idea","name":"Find the lowest effective doses of both drugs in a combination, not the highest tolerated","route":"/ideas/idea-tr2-combo-dose-matrix/"}],"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"}],"bottleneck":[{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}]}}