CONFIRM

• Research type

  Research Study

• Full title

  CheckpOiNt blockade For Inhibition of Relapsed Mesothelioma (CONFIRM): A Phase III Trial to Evaluate the Efficacy of Nivolumab in Relapsed Mesothelioma

• IRAS ID

  211270

• Contact name

  Kelly Cozens

• Contact email

  kc8@soton.ac.uk

• Sponsor organisation

  University of Southampton

• Eudract number

  2016-003111-35

• Duration of Study in the UK

  4 years, 11 months, 30 days

• Research summary

  Summary of Research

  The UK has the highest incidence of mesothelioma. The incidence has risen by 497% since the late 1970’s and is increasing worldwide due to continued mining and use of asbestos. For patients with mesothelioma who have relapsed after taking pemetrexed and cisplatin, there is currently no standard treatment, making this an urgent unmet need. Recent trials in this area have not found an effective treatment that improves overall survival.
  Following a debate in the House of Lords, a national survey assessing the research priorities in mesothelioma found that ‘exploiting the potential of immunotherapy’ was a top priority. This trial was designed in response to that survey. It uses the immunotherapy agent nivolumab which blocks programmed cell death 1 (PD-1) receptor on activated T-cells (a type of white blood cell forming part of the immune system). Early research has found a dependency of mesothelioma on the PD-1 checkpoint. By attaching to PD-1, nivolumab blocks its action (checkpoint inhibition), preventing it from turning off the T-cell, and therefore allowing the immune system to work. PD-1 checkpoint inhibition has revolutionised the treatment of melanoma and it is hoped to be as effective in mesothelioma.
  This trial is a randomised, double blind placebo controlled trial of patients with mesothelioma who are third relapse following a platinum based chemotherapy treatment. Patients will be randomised in a 2:1 ratio (nivolumab: placebo). 332 patients will be recruited from 25 UK centres over a four-year period with the last patient having a minimum of 6 months follow up. All patients will be on treatment for 12 months unless they progress or withdrawal prior to this. Clinic visits will occur every 12 weeks, mirroring standard care. Data following progression will be obtained from the NHS Information Centre.

  Summary of Results

  Background Mesothelioma is a cancer in the lining of organs (usually lung). It is often caused by exposure to asbestos. Diagnoses of mesothelioma are increasing, and survival tends to be short. Mesothelioma is normally treated with chemotherapy, but when this stops working there are no treatments recommended for use. Nivolumab is a treatment designed to help the immune system recognise and fight mesothelioma. Nivolumab has shown signs of benefit in smaller trials, but CONFIRM was designed to test it on a larger scale.

  Trial design
  Participants with mesothelioma who had previously received chemotherapy were recruited from across the UK between 2017 and 2020. The 332 participants were randomly allocated to receive nivolumab or placebo as an infusion. These were given every two weeks until either the mesothelioma got worse, the participant died, the participant or doctor wanted to stop, or until 12 months of treatment was completed. The trial measured how long participants lived for, how long it took for their mesothelioma to worsen, and what unwanted symptoms participants had.

  Results
  The CONFIRM trial found that participants who received nivolumab tended to go longer without their mesothelioma worsening (2.9 months compared to 1.6 months on average). Although the finding was less strong, it also appeared that participants who received nivolumab tended to live longer (9.5 months compared to 6.8 months on average). Slightly more participants experienced fatigue with nivolumab (39%) compared to placebo (31%). Approximately 1 participant out of 12 experienced an infusion related reaction when receiving nivolumab. The most common symptoms (diarrhoea, constipation, fatigue) were experienced equally in each group. Anaemia, shortness of breath and rashes were seen more in the nivolumab group. The preliminary results of the study were released in 2021 and may be found here: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbaNKhM2veQCpNbb8U3lc6HRgckYYYkT-2BdCrXK-2BQazlz-2BzF50bKh8G6kh2boMHfDKjg-3D-3DtPWN_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKeCNDrpctIPMGg8VAOCHdjcKy1SZf4v1MYsWBKtYbcDJf8igj8E7Vku-2BvoWzGRcEYuTwVpK8nAOJ5GEwB8YrUmPwJEuonG-2F7BeSVmtVGCgGVQi5gLGhs7jF9a3f-2BHe6tfge-2BMsSlZi2-2BqBAFF-2FMMq25KhqesP8fhrac9-2F4DpCrIQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C64ba748f56734fdafac108db0e88e8fc%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638119753415592291%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=kplYr0v1hIYhKvg%2Bi08QEiA%2F5FQJyojfq6%2FDbA5fUnE%3D&reserved=0

  Conclusions
  The final results suggest that nivolumab may be of benefit to people with mesothelioma, helping to delay the worsening of mesothelioma and extending survival. Further work will look into whether features of the mesothelioma can be used to predict who benefits most from nivolumab.

• REC name

  West Midlands - Edgbaston Research Ethics Committee

• REC reference

  16/WM/0472

• Date of REC Opinion

  6 Dec 2016

• REC opinion

  Further Information Favourable Opinion