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Non-Small Cell Lung CancerPhase 2NCT02664935

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer

A Phase 2 study testing AZD4547, Vistusertib and Palbociclib in people with Non-Small Cell Lung Cancer and Carcinoma, Squamous Cell, run by University of Birmingham at 25 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The trial consists of a series of parallel multi-centre single arm phase II trial arms, each testing an experimental targeted drug in a population stratified by multiple pre-specified actionable target putative biomarkers. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AZD4547, Vistusertib and Palbociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
423 participants
Where
25 sitesUnited Kingdom
Study dates
13 May 2015to 29 Nov 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Prior anti-cancer treatment:
  • Patients who refuse any standard of care first line therapy, are eligible to receive National Lung Matrix Trial treatment as first line therapy, providing they explicitly consent to this effect.
  • Patients who have previously consented to and received standard of care first line therapy must have completed all standard of care therapy that the treating oncologist thinks is appropriate. As a minimum patients must have failed one or more lines of treatment (either radiological documentation of disease progression or due to toxicity). Patients whose disease has increased in size but is not classed as progressive disease as per RECIST criteria, will be eligible. Patients with no change at all in dimension of disease (i.e. true stability) after first line therapy will not be eligible.
  • Patients who have progressed after surgical resection and adjuvant therapy will be eligible for entry without the need for the administration of first line metastatic therapy.
  • Patients will also be eligible without the necessity for first line regimen if they have relapsed within 6 months of completion of definitive chemoradiation.
  • Consented and provided an adequate specimen to adequately characterise the molecular genotype of the tumour in the molecular pre-screening according to the molecular exclusion rules (see Section 6.4 for definition of an adequate sample).
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  • Histological or cytologically confirmed NSCLC stage III (not suitable for radical radiotherapy or surgery) or stage IV. This includes patients who may have abnormal histology, but IHC strongly support either squamous cell carcinoma (p63 positivity) or adenocarcinoma (Thyroid transcription factor 1 [TTF1] positivity). If a physician and pathologist are convinced after multi-disciplinary review that the patient has stage III or IV NSCLC but where all the IHC is negative and the morphology does not distinguish a specific sub-type, these patients will be eligible for non-histology specific cohorts.
  • CT or MRI scan of head, chest and abdomen within 28 days of treatment demonstrating measurable disease as per RECIST version 1.1 (see Appendix 1: Response Evaluation Criteria in Solid Tumours Version 1.1). (The same imaging modality must be used throughout treatment).
  • Adequate haematological function within 7 days of treatment.
  • Haemoglobin ≥ 90 g/L.
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
  • Platelets ≥ 100 x 109/L.
  • Adequate hepatic function within 7 days of treatment in patients with no liver metastasis (see arm specific entry criteria for adequate hepatic function in patients with liver metastases).
  • Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN). (Note that this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology), who may be allowed inclusion at the discretion of the local Investigator).
  • Alanine transferase (ALT) ≤ 2.5 x ULN.
  • Aspartate transferase (AST) ≤ 2.5 x ULN.
  • Adequate renal function within 7 days of treatment.
  • Creatinine clearance (CLcr) >50 ml/min (measured or calculated by Cockcroft and Gault equation - see Appendix 4: Cockcroft Gault Formula - Creatinine Clearance). If calculated CLcr is <50 ml/min a direct measurement of glomerular filtration rate (GFR) such as EDTA may be performed. If the value is >50 ml/min the patient is eligible.
  • Age ≥ 18 years.
  • Females must agree to use adequate contraceptive measures (as defined in Section 6.3), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • Women aged under 50 years old would be consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution.
  • Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

Who cannot join

  • Major surgery (excluding placement of vascular access) within 4 weeks prior to treatment.
  • Nausea, vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease) that would preclude adequate absorption.
  • Any psychological, familial, sociological or geographical condition hampering protocol compliance.
  • Concurrent malignancies or invasive cancers diagnosed within past 3 years except for adequately treated basal cell carcinoma of the skin and in situ carcinoma of the uterine cervix.
  • Judgement by the local Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  • Any unresolved toxicity of grade 2, 3 or 4 from previous treatment (excluding alopecia) at Registration (see CTCAE - Appendix 3: Common Toxicity Criteria Gradings).
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  • Patients who have previous symptomatic brain metastases or spinal cord compression are excluded unless they have had adequate treatment, no evidence of progression or symptoms, and have had no requirement for steroid treatment in the previous 28 days before commencement of trial treatment.
  • Patients with asymptomatic brain metastases picked up at screening CT scan are not excluded providing that in the view of the local Investigator they do not require immediate radiotherapy or surgical intervention, and have had no requirement for steroid treatment in the previous 28 days before commencement of trial treatment.
  • As judged by the local Investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus. Screening for chronic conditions is not required.
  • Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to registration).
  • Cardiac exclusion criteria, performance status and prior treatment washout periods are detailed within the National Lung Matrix Trial arm-specific eligibility criteria.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United Kingdom25 sites

  • Aberdeen Royal Infirmary

    Aberdeen

  • Belfast City Hospital, Belfast Health and Social Care Trust

    Belfast

  • Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B15 2GW

  • Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust

    Birmingham

  • University Hospitals Bristol NHS Foundation Trust

    Bristol

  • Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Velindre Cancer Centre, Velindre NHS Trust

    Cardiff, CF14 2TL

  • Colchester General Hospital

    Colchester

  • Edinburgh Cancer Centre, Western General Hospital

    Edinburgh, EH4 2XU

  • Royal Devon and Exeter Hospital

    Exeter

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • St. James' University Hospital, Leeds Teaching Hospital NHS Trust

    Leeds, LS9 7TF

  • Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust

    Leicester

  • Royal Marsden Hospital, The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Charing Cross Hospital, Imperial College Healthcare NHS Trust

    London

  • Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust

    London

  • St Bartholomew's Hospital, Barts Health NHS Trust

    London

  • University College Hospital, University College London Hospitals NHS Foundation Trust

    London

  • Maidstone Hospital

    Maidstone

  • The Christie Hospital, The Christie NHS Foundation Trust

    Manchester

  • Clatterbridge Cancer Centre

    Metropolitan Borough of Wirral, CH63 4JY

  • Sir Bobby Robson Cancer Trial Research Centre, The Newcastle upon Tyne Hospitals

    Newcastle, NE7 7DN

  • Churchill Hospital, Oxford University Hospitals NHS Foundation Trust

    Oxford

  • Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield

  • Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

    Southampton, SO16 6YD

Other trials in United Kingdom

About this study

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

The trial consists of a series of parallel multi-centre single arm phase II trial arms, each testing an experimental targeted drug in a population stratified by multiple pre-specified actionable target putative biomarkers. The primary objective is to evaluate whether there is a signal of activity in each drug-(putative)biomarker cohort separately. A Bayesian adaptive design is adopted to achieve this objective and statistical details are given in the Protocol.

Read the detailed description

The trial is primarily an enrichment putative biomarker design, including patients who are positive for at least one of the actionable targets included in the trial. Patients who are positive for just one putative biomarker will receive the experimental targeted drug specific for that putative biomarker. Putative biomarkers within each drug cohort have been chosen such that in the majority of cases it is not expected that patients will be positive for two or more putative biomarkers within the same drug. In the rare situation that patients are positive for two or more putative biomarkers relevant across different drugs, treatment will be allocated in accordance with the following strategy:

  • All amplifications and rearrangements will be treated with targeted agent appropriate to them irrespective of concomitant mutations. This will yield crucial predictive biomarker information.
  • For concomitant mutations decisions will be made by the Chief Investigator on a case-by-case basis and based on close consideration of pathway preference and likely dominance of one signal pathway over another together with any pre-clinical efficacy studies that address the activity of the drugs in the presence of concomitant mutations. A trumping strategy has been devised for this purpose.
Being tested
AZD4547, Vistusertib, Palbociclib, Crizotinib, Selumetinib
Keywords
NSCLC, Lung Cancer, Adenocarcinoma, Matrix, SMP2, Umbrella Trial Design, Multi-arm
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Adenocarcinoma, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD4547Drug

    FGFR Inhibitor

  • VistusertibDrug

    Also called AZD2014

    MTORC1/2 Inhibitor

  • PalbociclibDrug

    CDK4/6 Inhibitor

  • CrizotinibDrug

    ALK/MET/ROS1 Inhibitor

  • SelumetinibDrug

    Also called AZD6244

    MEK Inhibitor

  • DocetaxelDrug

    Taxane, anti-mitotic cytotoxic chemotherapy

  • AZD5363Drug

    AKT Inhibitor

  • OsimertinibDrug

    Also called AZD9291

    EGFRm+ T790M+ Inhibitor

  • DurvalumabDrug

    Also called MEDI4736

    Anti-PDL1

  • SitravatinibDrug

    Also called MGCD516

    VEGFR Inhibitor

  • AZD6738Drug

    ATR inhibitor

Study groups in NCT02664935
Study groupRoleWhat they receive
Arm A: AZD4547ExperimentalAZD4547 - FGFR Inhibitor Route \& Formulation: Oral, Tablets Strengths: 20 \& 80mg Trial Dose \& Schedule: 80 mg BD, Continuous dosing, 21 day cycle.
Receives: Drug: AZD4547
Arm B: Vistusertib (AZD2014)ExperimentalVistusertib (AZD2014) - MTORC1/2 Inhibitor Route \& Formulation: Oral, Tablets Strengths: 25mg Trial Dose \& Schedule: 125 mg BD, Intermittent dosing (2 continuous days in 7), 28 day cycle.
Receives: Drug: Vistusertib
Arm C: PalbociclibExperimentalPalbociclib - CDK4/6 Inhibitor Route \& Formulation: Oral, Capsules Strengths: 75, 100 \& 125mg Trial Dose \& Schedule: 125 mg OD, Intermittent dosing (21 days on, 7 days off), 28 day cycle.
Receives: Drug: Palbociclib
Arm D: CrizotinibExperimentalCrizotinib - ALK Inhibitor Route \& Formulation: Oral, Capsules Strengths: 200 \& 250mg Trial Dose \& Schedule: 250 mg BD, Continuous dosing, 21 day cycle.
Receives: Drug: Crizotinib
Arm E: Selumetinib & DocetaxelExperimentalAZD6244 (Selumetinib) - MEK Inhibitor Route \& Formulation: Oral, Capsules Strengths: 25mg Trial Dose \& Schedule: 75 mg BD, Continuous dosing, 21 day cycle. Docetaxel - Chemotherapy Route \& Formulation: IV infusion over 30-60 minutes, concentrate for solution for infusion. Trial Dose \& Schedule: 75 mg/m2, 3-weekly, 21 day cycle.
Receives: Drug: Selumetinib; Drug: Docetaxel
Arm F: AZD5363ExperimentalAZD5363 - AKT Inhibitor Route \& Formulation: Oral, Tablets Strengths: 80 \& 200mg Trial Dose \& Schedule: 480 mg BD, Intermittent dosing (4 days on, 3 days off), 28 day cycles.
Receives: Drug: AZD5363
Arm G: Osimertinib (AZD9291)ExperimentalOsimertinib (AZD9291) - EGFRM+ and T790M+ Inhibitor Route \& Formulation: Oral, Tablets Strengths: 80mg Trial Dose \& Schedule: 80 mg OD, Continuous dosing, 21 day cycles.
Receives: Drug: Osimertinib
Arm NA: Durvalumab (MEDI4736)ExperimentalDurvalumab (MEDI4736) - Anti-PDL1 Route \& Formulation: IV Infusion, Lyophilized powder for solution for infusion Strengths: Vial containing 200mg Trial Dose \& Schedule: 10 mg/kg IV, 2-weekly.
Receives: Drug: Durvalumab
Arm H: SitravatinibExperimentalSitravatinib - VEGFR Inhibitor Route \& Formulation: Oral, Capsules Strengths: 10 \& 40mg Trial Dose \& Schedule: 120 mg OD, Continuous dosing, 21 day cycles.
Receives: Drug: Sitravatinib
Arm J: AZ6738 & DurvalumabExperimentalAZD6738 - ATR Inhibitor Route \& Formulation: Oral, Tablets Strengths: 20mg, 80mg, 100mg Trial Dose \& Schedule: 240 mg twice daily (BD) on days 15-28 of 28 day cycle. Durvalumab (MEDI4736) - Anti-PDL1 Route \& Formulation: IV Infusion, Lyophilized powder for solution for infusion Strengths: Vial containing 500mg Trial Dose \& Schedule: 1500mg on day 1 of each 28 day cycle
Receives: Drug: Durvalumab; Drug: AZD6738

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response (OR)

    CT scans every 6 weeks from baseline until disease progression (Primary outcome for all Trial Arms except Arm C). Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months.

    Measured: From baseline until disease progression, assessed up to 18 months.

  2. Progression-free survival time (PFS)

    Defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression (Primary Outcome for Arm C only). Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression. Investigators expect patients to participate in the study for a maximum of 18 months, however, cannot guarantee that some patients may participate over 18 months.

    Measured: From date of commencement of trial treatment to date of CT scan when progressive disease first recorded or date of death without previously recorded progression, assessed up to 18 months.

  3. Durable clinical benefit (DCB)

    A patient will be defined as experiencing DCB if they remain free of disease progression at their fourth CT or MRI scan since treatment start date, i.e. approximately 24 weeks, or at any scan after 24 weeks that shows the patient free of disease progression (co-primary outcome for all Trial Arms except Arm C \& G)

    Measured: From baseline until the first scan after 24 weeks showing the patient free of disease progression.

Secondary outcomes (4)

  1. Best percentage change in sum of target lesion diameters (PCSD)

    At each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months.

    Measured: From baseline until disease progression, assessed up to 18 months.

  2. Time to Progression (TTP)

    This is defined as the time from commencement of trial treatment to the date of the CT scan when progressive disease first recorded. Patients with no recorded progression at the time of analysis or who die without recorded progression will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months.

    Measured: The time from commencement of trial treatment to the date of the CT scan when progressive disease first recorded, assessed up to 18 months.

  3. Overall survival time (OS)

    This is defined as the time of commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months.

    Measured: From time of commencement of trial treatment until date of death, assessed up to 18 months.

  4. Adverse Events (AE)

    Adverse events will be recorded in relation to each cycle of treatment and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The incidence of each adverse event (all grades and grade 3/4) will be reported as a per-patient-cycle rate and as a per-patient rate. Investigators expect patients to participate in the study for a maximum of 18 months, however cannot guarantee that some patients may participate over 18 months.

    Measured: From date of informed consent to trial treatment until 28 days after the last administration of the last treatment, assessed up to 18 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2016 (estimated)
  2. Study start13 May 2015
  3. Primary completion29 Nov 2023
  4. Study completion29 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
423 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02664935
Sponsor's protocol ID
RG_14-072
Other IDs
2014-000814-73, ISRCTN38344105, 2014
Status last verified
Apr 2026
First submitted
5 Jan 2016
Last updated
28 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: For NLMT data, scientifically sound proposals from appropriately qualified Research Groups will be considered for data sharing. Requests should be made by returning a completed Data Sharing Request Form and curriculum vitae of the lead applicant and statistician to newbusiness@trials.bham.ac.uk. The Data Sharing Request Form captures information on the specific requirements of the research, the statistical analysis plan, and the intended publication schedule.

Publications

  • Middleton G, Crack LR, Popat S, Swanton C, Hollingsworth SJ, Buller R, Walker I, Carr TH, Wherton D, Billingham LJ. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer. Ann Oncol. 2015 Dec;26(12):2464-9. doi: 10.1093/annonc/mdv394. Epub 2015 Sep 25.

    PubMed 26410619

  • Middleton G, Robbins HL, Fletcher P, Savage J, Mehmi M, Summers Y, Greystoke A, Steele N, Popat S, Jain P, Spicer J, Cave J, Shaw P, Gilligan D, Power D, Fennell D, Bajracharya M, McBride DJ, Maheswari U, Frankell AM, Swanton C, Beggs AD, Billingham L. A phase II trial of mTORC1/2 inhibition in STK11 deficient non small cell lung cancer. NPJ Precis Oncol. 2025 Mar 11;9(1):67. doi: 10.1038/s41698-025-00838-4.

    PubMed 40069402

  • Middleton G, Fletcher P, Popat S, Savage J, Summers Y, Greystoke A, Gilligan D, Cave J, O'Rourke N, Brewster A, Toy E, Spicer J, Jain P, Dangoor A, Mackean M, Forster M, Farley A, Wherton D, Mehmi M, Sharpe R, Mills TC, Cerone MA, Yap TA, Watkins TBK, Lim E, Swanton C, Billingham L. The National Lung Matrix Trial of personalized therapy in lung cancer. Nature. 2020 Jul;583(7818):807-812. doi: 10.1038/s41586-020-2481-8. Epub 2020 Jul 15.

    PubMed 32669708

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD4547, Vistusertib and Palbociclib in people with Non-Small Cell Lung Cancer and Carcinoma, Squamous Cell, run by University of Birmingham at 25 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response (OR) (time frame: From baseline until disease progression, assessed up to 18 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02664935, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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