# Multi-arm, multi-stage trials to answer which order to give approved drugs

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

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- STAMPEDE trial: https://www.stampedetrial.org/

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- terms: [ADC sequencing](https://onco.cc/terms/adc-sequencing/), [Basket, umbrella, and platform trials](https://onco.cc/terms/basket-umbrella-platform/)
- bottlenecks: [Incentives reward me-too drugs and marginal gains](https://onco.cc/bottlenecks/b-incentive-misalignment/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)

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