{"entity":{"id":"idea-tr1-mams-for-sequencing-questions","kind":"idea","name":"Multi-arm, multi-stage trials to answer which order to give approved drugs","aka":[],"tldr":"Several drugs are approved for the same cancer, but nobody tests which order works best because no company benefits from the answer. Public multi-arm trials could settle these questions efficiently.","summary":"Cooperative groups run multi-arm multi-stage (MAMS) trials comparing sequences of already-approved agents (e.g., ADC then checkpoint inhibitor versus the reverse; endocrine-CDK4/6 sequencing; TKI order in RCC), with interim futility dropping of arms and OS or TTF across the sequence as the primary endpoint. Drug supply comes from companies under a neutral-access agreement; funding from payers and public agencies who bear the cost of wrong sequences.","asOf":"2026-09-08","links":[{"label":"STAMPEDE trial","url":"https://www.stampedetrial.org/"}],"tags":[],"related":[],"cancers":["rcc","breast-hr-positive","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["adc-sequencing","basket-umbrella-platform"],"trials":[],"people":[],"bottlenecks":["b-trial-design","b-incentive-misalignment"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Sequencing MAMS trials will identify orderings that improve OS or reduce cost by a clinically meaningful margin in at least half of the indications tested.","rationale":"Sequencing decisions currently rest on cross-trial inference and marketing. STAMPEDE showed MAMS can answer several questions in one structure; payers have a direct incentive to fund it.","test":"Launch one sequencing MAMS in a cancer with three or more approved second-line options and report the first interim arm decisions within three years.","maturity":"early-clinical","actor":"research","cost":"large","horizonYears":5},"route":"/ideas/idea-tr1-mams-for-sequencing-questions/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"term":[{"id":"adc-sequencing","kind":"term","name":"ADC sequencing","route":"/terms/adc-sequencing/"},{"id":"basket-umbrella-platform","kind":"term","name":"Basket, umbrella, and platform trials","route":"/terms/basket-umbrella-platform/"}],"bottleneck":[{"id":"b-incentive-misalignment","kind":"bottleneck","name":"Incentives reward me-too drugs and marginal gains","route":"/bottlenecks/b-incentive-misalignment/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}]}}