A trial of nivolumab, ipilimumab and chemotherapy for advanced lung cancer (CA209227)

Cancer type:

Lung cancer
Non small cell lung cancer
Secondary cancers

Status:

Results

Phase:

Phase 3

This trial was for people with non small cell lung cancer (NSCLC) that had spread to another part of the body.

This trial was open for people to join between August 2015 and November 2016.

These results were published in 2018 . 

More about this trial

Chemotherapy is the usual treatment for advanced NSCLC. But for some people this might not work well. This is because of certain proteins on the cancer cells. These proteins can stop the body’s immune system attacking cancer cells. 

One protein is PD-L1. Nivolumab is a targeted cancer drug. It works by blocking PD-L1. We knew from research that nivolumab helped people with NSCLC.

In this trial the team looked at the following treatments:

  • nivolumab
  • nivolumab and ipilimumab
  • nivolumab and chemotherapy
  • chemotherapy
The chemotherapy used was pemetrexed combined with either cisplatin or carboplatin. 
 
The number of gene changes (mutations Open a glossary item) in the cancer is called the tumour mutational burden. When there is a lot of gene changes this is called a high mutational burden. When there is a few this is called a low mutational burden.
 
Research suggests that the mutational tumour burden could be used to predict how well treatment would work. 
 
The main aims of this trial were to find:
  • how well the above treatments worked for NSCLC
  • how safe the above treatments were for people with NSCLC
  • how acceptable people found the above treatments
The team also wanted to find out if the tumour mutational burden could be used to find out how well treatment was working or might work.  

Summary of results

The team found there was a benefit of having ipilimumab and nivolumab for people with non small cell lung cancer (NSCLC). 
 
About this trial
This was an international phase 3 trial. 1,739 people worldwide joined the trial. 
 
It was a randomised trial. Everyone who took part were put into a treatment group. Neither they or their doctor could choose which group they were in.
 
The treatment groups were:
  • nivolumab and ipilimumab
  • nivolumab
  • chemotherapy (pemetrexed combined with either cisplatin or carboplatin)
Before being put into a treatment group the team looked at the sample of cancer tissue (biopsy Open a glossary item) from everyone when they were diagnosed. 
 
The team looked at how much of the whole sample of cancer tissue had the protein PD-L1. 
 
They also looked at the number of gene changes (mutations) in the cancer (tumour mutational burden).
 
PD-L1
Of the 1,189 people whose cancer tissue sample had the PDL-1 protein in at least 1 part of every 100 parts (1%):
  • 396 had nivolumab and ipilimumab
  • 396 had nivolumab
  • 397 had chemotherapy 

And of the 550 people whose cancer tissue sample had PDL-1 protein in less than 1 part of every 100 parts (less than 1%):

  • 187 had nivolumab and ipilimumab
  • 177 had nivolumab and chemotherapy
  • 186 had chemotherapy
Tumour mutational burden
444 people had a high number of gene changes (high mutational tumour burden). Of these they were able to look at 299 people of whom:
  • 139 had nivolumab and ipilimumab
  • 160 had chemotherapy 
Results
These results are mainly looking at how treatment worked for people whose cancer had a high mutational tumour burden. 
 
The average follow up was just over 11 months (11.2).
 
Results for everyone
The team looked at how many people were alive and had no sign of their cancer 1 year after treatment. They found it was higher in those who had nivolumab and ipilimumab than those who had nivolumab and chemotherapy. It was:
  • just under 31 out of every 100 people (30.9%) in the nivolumab and ipilimumab group
  • 17 out of every 100 people (17%) in the chemotherapy group

Results for those with a high number of gene changes (high mutational tumour burden)
The team looked at the overall number of people whose cancer had responded to treatment. They found it was:
  • just over 45 people out of every 100 (45.3%) in the nivolumab and ipilimumab group
  • just under 27 people out of every 100 (26.9%) in the chemotherapy group

The team looked at how many people were alive and had no sign of their cancer 1 year after treatment. They found it was:
  • just over 42 out of every 100 people (42.6%) in the nivolumab and ipilimumab group
  • just over 13 out of every 100 people (13.2%) in the chemotherapy group

The average length of time people were alive and had no sign of their cancer was:
  • just over 7 months (7.2) in the nivolumab and ipilimumab group
  • 5 ½ months in the chemotherapy group

The amount of PD-L1 gene change in the cancer didn’t make a difference to these results. 
 
Results for those with a low number of gene changes (low mutational tumour burden)
The average length of time people were alive and had no sign of their cancer was:
  • just over 3 months (3.2) for those who had nivolumab and ipilimumab
  • 5½ months for those who had chemotherapy
Side effects
The number of severe side effects reported was less in the nivolumab and ipilimumab group than the chemotherapy group. 
 
For those having nivolumab and ipilimumab just over 31 out of every 100 side effects reported (31.2%) were severe.
 
For those having chemotherapy just over 36 out of every 100 side effects reported (36.1%) were severe. 
 
Conclusion
The trial team concluded that these results confirm nivolumab combined with ipilimumab is a good first treatment for people with advanced non small cell lung cancer (NSCLC). And whose cancer has a high number of gene changes (mutational tumour burden). 
 
The number of gene changes in the cancer (mutational tumour burden) is an important and separate sign of how well treatment works for advanced NSCLC.
 
Research is continuing into other parts of this trial. When these results become available this summary will be updated. 
 
Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr David Spicer

Supported by

Bristol-Myers Squibb
Experimental Cancer Medicine Centre (ECMC)
Ono Pharmaceutical Co. Ltd

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Freephone 0808 800 4040

Last review date

CRUK internal database number:

14094

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

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