{"entity":{"id":"idea-tr2-neoadjuvant-combo-platform","kind":"idea","name":"Pre-surgery platform trials that test combinations on pathological response in months","aka":[],"tldr":"Give drug combinations before surgery and measure how much tumour remains at resection; that answer arrives in months. A standing neoadjuvant platform with a shared control arm, as I-SPY 2 runs in breast cancer, would test combinations quickly in lung, bladder, melanoma, head and neck and oesophago-gastric cancer.","summary":"I-SPY 2 established graduation of arms by pathological complete response in breast cancer. The same model applies to lung, bladder, melanoma, head and neck and oesophago-gastric cancer where neoadjuvant therapy is now standard. Each cancer needs a standing neoadjuvant platform with a shared control arm and pre-agreed rules for graduating an arm to a confirmatory trial.","asOf":"2026-09-08","links":[{"label":"I-SPY trials","url":"https://www.ispytrials.org/"}],"tags":[],"related":["major-pathological-response","neoadjuvant-io-response-adapted"],"cancers":["esophageal","head-and-neck","nsclc","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","rcb","basket-umbrella-platform"],"trials":["keynote-522","nadina"],"people":[],"bottlenecks":["b-combination-space","b-trial-design"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Neoadjuvant platforms will screen at least five combination arms per year per cancer, with pathological response predicting event-free survival well enough that graduated arms confirm in phase 3 at least 60% of the time.","rationale":"Pathological complete response and major pathological response correlate with survival in breast, lung and melanoma, and the neoadjuvant window allows paired biopsies that explain why a combination did or did not work.","test":"Open a neoadjuvant platform in one cancer without one (oesophago-gastric or head and neck), graduate two arms by pathological response, and track confirmation.","maturity":"being-tested-at-scale","actor":"research","cost":"large","horizonYears":3},"route":"/ideas/idea-tr2-neoadjuvant-combo-platform/","neighbours":{"term":[{"id":"basket-umbrella-platform","kind":"term","name":"Basket, umbrella, and platform trials","route":"/terms/basket-umbrella-platform/"},{"id":"major-pathological-response","kind":"term","name":"Major pathological response (MPR)","route":"/terms/major-pathological-response/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"pairing":[{"id":"neoadjuvant-io-response-adapted","kind":"pairing","name":"Neoadjuvant immunotherapy → response-adapted adjuvant","route":"/pairings/neoadjuvant-io-response-adapted/"}],"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"resectable-nsclc","kind":"cancer","name":"Resectable stage I to III non-small-cell lung cancer","route":"/cancers/resectable-nsclc/"}],"trial":[{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/"},{"id":"nadina","kind":"trial","name":"NADINA","route":"/trials/nadina/"}],"bottleneck":[{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"idea":[{"id":"idea-tr2-bandit-allocation","kind":"idea","name":"Let the trial learn: response-adaptive allocation across many combination arms","route":"/ideas/idea-tr2-bandit-allocation/"},{"id":"idea-tr2-window-of-opportunity-triplets","kind":"idea","name":"Two-week pre-operative windows to compare combination biology head to head","route":"/ideas/idea-tr2-window-of-opportunity-triplets/"}],"roadmap":[{"id":"surgery-roadmap","kind":"roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/"},{"id":"trial-modernisation-roadmap","kind":"roadmap","name":"Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on","route":"/roadmaps/trial-modernisation-roadmap/"}]}}