Evidence map›Paper›PMID 40069402›Full record

ArticleNPJ precision oncology2025

A phase II trial of mTORC1/2 inhibition in STK11 deficient non small cell lung cancer.

Gary Middleton, Helen L Robbins, Peter Fletcher, Joshua Savage, Manita Mehmi, Yvonne Summers, Alastair Greystoke, Nicola Steele, Sanjay Popat, Pooja Jain and 13 more

Registry-linked trialAbstract read
In one paragraph

Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02664935 (National Lung Matrix Trial), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02664935 phase2completednot on this map

National Lung Matrix Trial: Multi-drug, Genetic Marker-directed, Non-comparative, Multi-centre, Multi-arm Phase II Trial in Non-small Cell Lung Cancer

TypeinterventionalSponsorUniversity of BirminghamRan2015 to 2023Enrolled423ConditionsNon-Small Cell Lung Cancer, Carcinoma, Squamous Cell, AdenocarcinomaArmsAZD4547, Vistusertib, Palbociclib, Crizotinib, Selumetinib
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Current oncology (Toronto, Ont.) · 2026
    Review
  4. Article
  5. Immune checkpoint inhibitors have limited efficacy inTranslational lung cancer research · 2025
    Article
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Gary Middleton *University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. g.middleton@bham.ac.uk.
Helen L Robbins *University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Peter FletcherCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
Joshua SavageCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-0599-0245
Manita MehmiCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0001-8220-9331
Yvonne SummersThe Christie, Manchester, UK.
Alastair GreystokeNewcastle University, Newcastle, UK.
Nicola SteeleBeatson West of Scotland Cancer Centre, Glasgow, UK.
Sanjay PopatThe Royal Marsden Hospital, London, UK.
Pooja JainSt James's University Hospital, Leeds, UK.ORCID http://orcid.org/0000-0002-0645-8026
James SpicerKing's College London, Guy's Hospital, London, UK.
Judith CaveSouthampton University Hospitals NHS Trust, Southampton, UK.
Paul ShawVelindre Cancer Centre, Cardiff, UK.
David GilliganAddenbrooke's Hospital, Cambridge, UK.
Danielle PowerImperial College Healthcare NHS Trust, London, UK.
Dean FennellLeicester Royal Infirmary, Leicester, UK.
Maya BajracharyaIllumina Cambridge Ltd, Cambridge, UK.
David J McBrideIllumina Cambridge Ltd, Cambridge, UK.
Uma MaheswariIllumina Cambridge Ltd, Cambridge, UK.
Alexander M FrankellCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.
Charles SwantonCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.ORCID http://orcid.org/0000-0002-4299-3018
Andrew D BeggsUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Lucinda BillinghamCancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There are no current stratified medicine options for STK11-deficient NSCLC. STK11 loss mediates mTORC activation, GLUT1 up-regulation and increased glycolysis. This metabolic reprogramming might represent a therapeutic vulnerability targetable with mTORC1/2 inhibition. In arm B2 of the National Lung Matrix Trial 54 patients with NSCLC received vistusertib, of which 49 were STK11-deficient (30 with KRAS mutation (B2D), 19 without (B2S)). Objective response (OR) and durable clinical benefit (DCB) rates with 95% credible intervals (CrI) were estimated from posterior probability distributions generated using Bayesian beta-binomial conjugate analysis. In B2D, 2 per-protocol patients obtained OR (estimated true OR rate (95%CrI) 9.8% (2.4-24.3). Estimates of true DCB rate (95%CrI): B2D 24.4% (11.1-42.3), B2S 14.6% (3.6-34.7). Overall, vistusertib cannot be recommended in this context. Longitudinal ctDNA analysis demonstrates enrichment of SMARCA4 mutations post-treatment. In vitro studies show adaptive resistance to mTORC1/2 inhibition via AKT reactivation. (NCT02664935, ISRCTN38344105, EudraCT 2014-000814-73, 10 June 2015).

Identifiers

PMID40069402
PMCPMC11897347

What Socratic holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.