National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer
3 other identifiers
interventional
423
1 country
25
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started May 2015
Longer than P75 for phase_2 nonsmall-cell-lung-cancer
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 13, 2015
CompletedFirst Submitted
Initial submission to the registry
January 5, 2016
CompletedFirst Posted
Study publicly available on registry
January 27, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 29, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 29, 2023
CompletedApril 28, 2026
April 1, 2026
8.6 years
January 5, 2016
April 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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.
From baseline until disease progression, assessed up to 18 months.
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.
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.
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)
From baseline until the first scan after 24 weeks showing the patient free of disease progression.
Secondary Outcomes (4)
Best percentage change in sum of target lesion diameters (PCSD)
From baseline until disease progression, assessed up to 18 months.
Time to Progression (TTP)
The time from commencement of trial treatment to the date of the CT scan when progressive disease first recorded, assessed up to 18 months.
Overall survival time (OS)
From time of commencement of trial treatment until date of death, assessed up to 18 months.
Adverse Events (AE)
From date of informed consent to trial treatment until 28 days after the last administration of the last treatment, assessed up to 18 months.
Study Arms (10)
Arm A: AZD4547
EXPERIMENTALAZD4547 - FGFR Inhibitor Route \& Formulation: Oral, Tablets Strengths: 20 \& 80mg Trial Dose \& Schedule: 80 mg BD, Continuous dosing, 21 day cycle.
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.
Arm C: Palbociclib
EXPERIMENTALPalbociclib - 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.
Arm D: Crizotinib
EXPERIMENTALCrizotinib - ALK Inhibitor Route \& Formulation: Oral, Capsules Strengths: 200 \& 250mg Trial Dose \& Schedule: 250 mg BD, Continuous dosing, 21 day cycle.
Arm E: Selumetinib & Docetaxel
EXPERIMENTALAZD6244 (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.
Arm F: AZD5363
EXPERIMENTALAZD5363 - 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.
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.
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.
Arm H: Sitravatinib
EXPERIMENTALSitravatinib - VEGFR Inhibitor Route \& Formulation: Oral, Capsules Strengths: 10 \& 40mg Trial Dose \& Schedule: 120 mg OD, Continuous dosing, 21 day cycles.
Arm J: AZ6738 & Durvalumab
EXPERIMENTALAZD6738 - 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
Interventions
Anti-PDL1
Eligibility Criteria
You may not qualify if:
- 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.
- 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).
- Alanine transferase (ALT) ≤ 2.5 x ULN.
- Aspartate transferase (AST) ≤ 2.5 x ULN.
- Adequate renal function within 7 days of treatment.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Birminghamlead
- Cancer Research UKcollaborator
- AstraZenecacollaborator
- Pfizercollaborator
- Experimental Cancer Medicine Centrescollaborator
- Mirati Therapeutics Inc.collaborator
Study Sites (25)
Aberdeen Royal Infirmary
Aberdeen, United Kingdom
Belfast City Hospital, Belfast Health and Social Care Trust
Belfast, United Kingdom
Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW, United Kingdom
Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust
Birmingham, United Kingdom
University Hospitals Bristol NHS Foundation Trust
Bristol, United Kingdom
Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ, United Kingdom
Velindre Cancer Centre, Velindre NHS Trust
Cardiff, CF14 2TL, United Kingdom
Colchester General Hospital
Colchester, United Kingdom
Edinburgh Cancer Centre, Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Royal Devon and Exeter Hospital
Exeter, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
St. James' University Hospital, Leeds Teaching Hospital NHS Trust
Leeds, LS9 7TF, United Kingdom
Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
Leicester, United Kingdom
Royal Marsden Hospital, The Royal Marsden NHS Foundation Trust
London, SW3 6JJ, United Kingdom
Charing Cross Hospital, Imperial College Healthcare NHS Trust
London, United Kingdom
Guy's Hospital, Guy's and St Thomas' NHS Foundation Trust
London, United Kingdom
St Bartholomew's Hospital, Barts Health NHS Trust
London, United Kingdom
University College Hospital, University College London Hospitals NHS Foundation Trust
London, United Kingdom
Maidstone Hospital
Maidstone, United Kingdom
The Christie Hospital, The Christie NHS Foundation Trust
Manchester, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Sir Bobby Robson Cancer Trial Research Centre, The Newcastle upon Tyne Hospitals
Newcastle, NE7 7DN, United Kingdom
Churchill Hospital, Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom
Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom
Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD, United Kingdom
Related Publications (3)
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.
PMID: 26410619BACKGROUNDMiddleton 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.
PMID: 40069402RESULTMiddleton 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.
PMID: 32669708RESULT
Related Links
- PL02.09 National Lung Matrix Trial (NLMT): First Results from an Umbrella Phase II Trial in Advanced Non-Small Cell Lung Cancer (NSCLC) Middleton, G. et al. Journal of Thoracic Oncology, Volume 14, Issue 10, S7
- MA06. 06 A Phase II Trial of Ceralasertib and Durvalumab in Advanced Non-Small Cell Lung Cancer (NSCLC) with and without RAS Mutations: Results of NLMT Arm J
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gary W Middleton
University of Birmingham
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 5, 2016
First Posted
January 27, 2016
Study Start
May 13, 2015
Primary Completion
November 29, 2023
Study Completion
November 29, 2023
Last Updated
April 28, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ANALYTIC CODE
- Time Frame
- Unending
- Access Criteria
- Requests will be reviewed independently by the Cancer Research UK Clinical Trials Unit (CRCTU) Directors at University of Birmingham in discussion with the Chief Investigator and relevant Trial Management Group and independent Trial Steering Committee. In making their decision the Director's Committee will consider the scientific validity of the request, the qualifications of the Research Group, the views of the Chief Investigator, Trial Management Group and Trial Steering Committee, consent arrangements, the practicality of anonymizing the requested data and contractual obligations. Where the CRCTU Directors and appropriate Trial Committees are supportive of the request, and where not already obtained, consent for data transfer will be sought from the Sponsor of the trial before notifying the applicant of the outcome of their request. It is anticipated that applicants will be notified of a decision within 3 months of receipt of the original request.
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.