# National Lung Matrix Trial

Source: https://onco.cc/trials/national-lung-matrix-trial/  
OnCo record `national-lung-matrix-trial` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The National Lung Matrix Trial was the United Kingdom's umbrella trial in lung cancer: thousands of patients were screened through the NHS and those with one of 22 rare genetic changes were offered a matching drug. Most cohorts did not clear the bar, which taught the field how hard single-target matching is outside the strongest drivers.

## Summary

The National Lung Matrix Trial opened in 2015, led by Gary Middleton at the University of Birmingham and fed by Cancer Research UK's Stratified Medicine Programme 2, which sequenced tumours from patients across the NHS with a 28-gene panel. Patients with one of the trial's actionable alterations and non-small-cell lung cancer that had progressed after first-line therapy entered one of 22 cohorts, each pairing a genetic change with one of eight drugs supplied by AstraZeneca and Pfizer: palbociclib, crizotinib, selumetinib with docetaxel, capivasertib, osimertinib, durvalumab, vistusertib and AZD4547. Each cohort used a Bayesian adaptive design with pre-set thresholds for response or durable benefit, so cohorts could be closed early or expanded.

The trial's main report, in Nature in 2020, covered more than 5,000 patients screened and around 300 treated across 19 cohorts. Few cohorts met their thresholds. Signals appeared where the drug matched a strong driver, and the trial confirmed the general finding of NCI-MATCH and Lung-MAP that many rarer alterations, especially loss-of-function changes and amplifications, do not predict benefit from a single targeted drug. A high proportion of screened patients could not enter because their disease had worsened or they had died before a slot opened, which quantified how slow tissue-based national screening was.

What it changed in Britain was infrastructure: it showed the NHS could run population-scale molecular screening feeding one trial, which fed directly into the design of DETERMINE and TARGET National, and it argued for combinations and for screening earlier in the disease. The trial's later cohorts, including ceralasertib with durvalumab in RAS-mutant and wild-type disease and mTORC1/2 inhibition in STK11-deficient cancers, were published in 2025 and 2026.

## Fields

- Kind: Trial
- Status: completed
- Last checked: 2026-09-17
- Also known as: NLMT; Lung Matrix; CRUK Stratified Medicine Programme 2
- Registry id: NCT02664935
- Phase: 2
- Setting: Advanced non-small-cell lung cancer after first-line treatment, screened nationally through the Cancer Research UK Stratified Medicine Programme: 22 biomarker-defined cohorts of eight targeted drugs
- Sponsor: University of Birmingham, funded by Cancer Research UK with drugs from AstraZeneca and Pfizer
- Result: Most of the 22 biomarker-drug cohorts did not meet their pre-set efficacy thresholds; the trial demonstrated national molecular screening and the limits of single-agent matching.

## Sources

- ClinicalTrials.gov NCT02664935: https://clinicaltrials.gov/study/NCT02664935
- Middleton et al., Nature 2020: the National Lung Matrix Trial of personalized therapy in lung cancer: https://doi.org/10.1038/s41586-020-2481-8

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [CDK4/6 inhibitors](https://onco.cc/technologies/cdk46-inhibitor/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [PI3K, AKT and mTOR inhibitors](https://onco.cc/technologies/pi3k-akt-mtor-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Capivasertib](https://onco.cc/drugs/capivasertib/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Durvalumab](https://onco.cc/drugs/durvalumab/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Palbociclib](https://onco.cc/drugs/palbociclib/), [Selumetinib](https://onco.cc/drugs/selumetinib/), [Vistusertib](https://onco.cc/drugs/vistusertib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- institutions: [Cancer Research UK](https://onco.cc/institutions/cruk/), [University Hospitals Birmingham / University of Birmingham Cancer Research Centre](https://onco.cc/institutions/birmingham-cancer-centre/)
- terms: [Basket, umbrella, and platform trials](https://onco.cc/terms/basket-umbrella-platform/), [Master protocol (platform, basket and umbrella trials)](https://onco.cc/terms/master-protocol/), [Seamless, adaptive and Bayesian trial designs](https://onco.cc/terms/seamless-adaptive/)
- bottlenecks: [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)

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