Multi-drug phase II trial in non-small cell lung cancer

Transcription

1 Multi-drug phase II trial in non-small cell lung cancer Sponsor: University of Birmingham Chief Investigator: Gary Middleton Chief Biostatistician: Lucinda Billingham Lead Investigators: Sanjay Popat, Timothy Yap, Yvonne Summers, James Spicer Trial Management Team at CRCTU: Laura Llewellyn, Dee Wherton, Susannah Brown, Kate Davies, Maria Sharif, Peter Fletcher, Ylenia Vigo, Ian Nutt SMP2 Team at Cancer Research UK: led by Rowena Sharpe and Catrin Middleton Trial Management Group: chaired by Sanjay Popat Trial Steering Committee: chaired by Richard Kaplan Current Pharma partners: AstraZeneca, Pfizer Contact: Website: 1

2 Background 2

3 Non-Small Cell Lung Cancer (NSCLC) In the UK, 46,000 people every year are diagnosed with lung cancer (Cancer Research UK Cancer Statistics website) Lung cancer is the most common cause of death worldwide with 1.59 million deaths in 2012 NSCLC is the most common type of lung cancer. 3

4 Treating NSCLC Traditionally doctors decide on how to treat a cancer by looking at what type of cancer it is, but this doesn t work for everyone The body is made up of trillions of cells, which all have a specific job. DNA is a set of instructions found in the genes inside each cell telling it what to do In tumours sometimes the instructions (DNA) can have mistakes. This is particularly true in lung cancer, where changes in the DNA are different from person to person By testing a small piece of tumour in the laboratory a change in the DNA sequence can be found in some patients. 4

5 The National Lung Matrix Trial Doctors look at which DNA change the patient s cancer has and then select the best drug option for that particular patient This is called precision medicine, stratified medicine or targeted therapy By testing a small piece of tumour in the laboratory, a change in the DNA sequence can be found in some patients Different drugs can target cancers with different DNA changes 5

6 Trial Design 6

7 Aims of the National Lung Matrix Trial We would like to: See how well each treatment works Find out more information about tumour shrinkage Find out more information about the safety of the drugs and associated side effects Collect blood samples to look at the tumour DNA present in the blood before, during and after treatment. This may enable us to identify which changes in the tumour DNA are linked to drug resistance Collect tissue to help us understand why some people benefit from treatment and others do not. 7

8 Trial Treatment Patients will be offered a drug depending on the specific gene (or DNA) change present within their cancer cells Patients will be placed into different groups (referred to as arms), depending on the drug they receive and also into different sub-groups (referred to as cohorts) depending on the type of NSCLC and gene change they have: Arm Drug Cohort DNA/gene change A AZD4547 A1 FGFR or FGFR3 mutation B Vistusertib (AZD2014) B1 B2 C Palbociclib C1 C2 C3 C4 C5 C6 TSC1 or TSC2 mutation STK11/LKB1 mutation or homozygous deletion Proficient Rb and homozygous p16 loss Proficient Rb and homozygous p16 loss Proficient Rb and CDK4 amplification Proficient Rb and CCND1 amplification Proficient Rb, STK11/LKB1 mutation or homozygous deletion, TSC1/TSC2 mutation, with activated KRAS/MAPK pathway Proficient Rb and KRAS mutation 8

9 Trial Treatment continued Arm Drug Cohort DNA change D Crizotinib D1 D2 D3 E Selumetinib & Docetaxel E1 E2 E3 F AZD5363 F1 F2 F3 F4 G NA Osimertinib (AZD9291) Durvalumab (MEDI4736) G1 NA1 MET amplification ROS1 gene fusions MET exon 14 mutation or deletion NF1 mutation NF1 mutation NRAS mutation PIK3CA mutation PIK3CA mutation PI3K/AKT deregulation PTEN loss or PTEN mutation EGFR mutation and T790M+ No gene change 9

10 Patients & Hospitals 10

11 Who can take part in the trial Patients aged at least 18 years with: Non-small cell lung cancer that is either squamous cell carcinoma or adenocarcinoma Cancer that has spread outside of the lung (stage 3) where further surgery or radiotherapy will not be curative, or cancer that has spread to another part of your body (stage 4) And have: Received at least one suitable standard treatment and the cancer has continued to grow Consented and given a tumour sample for the Stratified Medicine Programme 2 (SMP2) (Other more detailed entry criteria apply) 11

12 Who cannot take part in the trial Patients with: Cancer that has spread to the brain or is pressing on the spinal cord and requires treatment (steroids) Any other cancer in the last 3 years (except carcinoma of the cervix or basal cell skin cancer that has been successfully treated) Side effects from earlier cancer treatment (except hair loss) HIV, hepatitis B or hepatitis C Certain heart problems (depending on which treatment you receive) And have: Received major chemotherapy, surgery, radiotherapy or other anticancer treatment in the last 4 weeks (Other more detailed entry criteria apply) 12

13 Benefits for patients There is no guarantee that individual patients will benefit directly from taking part in the trial, however It is possible that the drugs may cause tumour shrinkage and/or prolong some patients lives Tests and treatment being used today were developed thanks to the help of patients who took part in research years ago Information from the National Lung Matrix trial will help to improve the treatment of other people with NSCLC in the future 13

14 Participating Hospitals The National Lung Matrix Trial is being run through all 18 UK Experimental Cancer Medicine Centres (ECMC) at 18 hospitals throughout the UK 10 additional hospitals have been approved for inclusion in areas of the UK with large populations of lung cancer patients not currently represented in the trial See the National Lung Matrix Trial website for up-to-date details on participating hospitals: 14

15 Trial Recruitment 15

16 Trial Recruitment Target Patients are placed into different groups (arms), depending on the specific drug they receive and also into different sub-groups (cohorts) depending on the type of NSCLC and gene change they have. Each cohort aims to recruit up to 30 patients: After the first 15 patients have been recruited, their safety data and trial results are reviewed, and the Trial Steering Committee decide whether the trial should continue recruiting in this cohort or stop. The overall trial recruitment target is 620 patients (correct at 01-Aug- 2017). 16

17 Cumulative & Monthly Recruitment Data as of 30 th June

18 Recruitment by Treatment Arm and Cohort Data as of 30 th June

19 Trial Management & Milestones 19

20 Who is organising and funding the trial Sponsor: University of Birmingham The company who takes overall responsibility for the quality assurance and conduct of the trial Clinical Trials Unit: Cancer Research UK Clinical Trials Unit Responsible for the design of, and day to day running of the trial, including analysis of trial results Chief Investigator: Professor Gary Middleton A named researcher who is responsible for the design & conduct of the research Funder: Cancer Research UK Provides a grant to the Sponsor and Clinical Trials Unit to enable the trial to run. (Doctors do not receive any payments for recruiting patients) Drug supply: AstraZeneca & Pfizer The current trial arms are testing drugs supplied free of charge by these two pharmaceutical companies 20

21 Who is overseeing the trial Operational Management Group: Oversight of the day to day management of the trial and decision making Trial Management Group: Monitor all aspects of the conduct and progress of the trial, patient safety and trial quality Multidisciplinary group including radiology, pathology, pharmacy & patient representation Trial Steering Committee: Provide overall supervision of the trial, monitor trial progress, safety, and make recommendations to continue, modify or stop the trial Medicines and Healthcare products Regulatory Agency (MHRA) Provide approval to run the trial, review relevant changes to the trial and safety data Research Ethics Committee Independently safeguard the rights, safety, dignity and well-being of research participants 21

22 Trial Milestones Year Milestone 2017 July: Major improvements to trial website June: 150 th patient recruited & funding approved for 2 new cohorts 2016 November: 100 th patient recruited June: Approval for funding for further 2 years & 2 new arms from Cancer Research UK March: 50 th patient recruited 2015 October: Additional Arm F & G opened to recruitment May: First patient recruited March: First hospital opened to recruitment (Newcastle) 2014 December: MHRA approval received November: Research ethics approval received October: Protocol Version 1 submitted for MHRA & research ethics approval August: Cancer Research UK Grant activated 2013 September: Cancer Research UK Clinical Trials Unit at Birmingham selected to run the trial with Prof Gary Middleton as the Chief Investigator 22

23 With Many Thanks to: The Cancer Research UK Clinical Trials Unit National Lung Matrix Trial Team The Cancer Research UK SMP2 Team Members of the National Lung Matrix Trial Management Group & Trial Steering Committee Members of the SMP2 Governance Board The NCRI Lung Clinical Studies Group All the Lead Investigators, Principal Investigators, clinical teams and research nurses at all sites The patients and their families 23

24 Thank You 24