Adjuvant canakinumab vs placebo in stages II-IIIB resected NSCLC
Research type
Research Study
Full title
A phase III, multicenter, randomized, double blind, placebo controlled study evaluating the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult subjects with stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) completely resected (R0) non-small cell lung cancer(NSCLC)
IRAS ID
236685
Contact name
Kent Yip
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2017-004011-39
Duration of Study in the UK
7 years, 6 months, 22 days
Research summary
This is a clinical research study to find out if the drug, canakinumab, is safe and effective in preventing the re-appearance of cancer in people who have had non-small cell lung cancer. Patients will already have had an operation to remove the primary cancer, followed by chemotherapy and radiation therapy (if applicable) depending on the severity of their disease at the time of original diagnosis.
Canakinumab is an antibody (a specific type of protein). It is able to bind to a naturally occurring agent of the inflammatory system called interleukin-1 beta (IL-1β). It works to lessen inflammation by blocking IL-1β activity. By blocking inflammation this may work against cancer growth. It is administered by the study team as an injection in the upper arm, upper leg or skin on the stomach. This is the first time it will be studied on its effectiveness and safety in cancer. It is approved for use in the UK for treatment of some inflammatory conditions and over 15,000 patients have received it to-date for these.
Eligible patients will have an equal chance of receiving either canakinumab or a placebo (a dummy drug substitute with no active ingredient). Study drug will be given every 3 weeks for a total of 18 cycles of treatment followed by an end of treatment visit. There are then 5 safety follow-up visits (every 28 days for 130 days after last study drug dose). Patients will be monitored for the reappearance of cancer for approximately 5 years after first dose of study drug at clinic visits every 6 months for years 2 and 3 and annually for years 4 and 5. Clinical visits will involve blood and urine samples and questionnaires about quality of life. Some visits also include CT or MRI scans and an ECG.
Lay Summary
How long Was This Trial
The trial began in March 2018 and ended in February 2023. It was planned for the participants to be in the trial for about 5 years after receiving the trial treatment. However, the sponsors decided to end the trial early as the initial analysis showed that ACZ885 did not have the expected effect on the advanced NSCLC.
Who Was In The Trial
1382 participants with advanced NSCLC entered in this trial. Participants’ ages ranged from 21 to 83 years. Their average age was 62 years.
Gender:
862 Men 520 Women.
Race:
78 White, 5 American Indian or Alaska Native, 484 Asian, 1 Multiple races, 7 Black or African American, 101 Missing.The participants could take part in this trial if they:
• had complete surgical removal of their cancer,
• had completed radiation or chemotherapy after the surgical removal of their cancer,
• had recovered from side effects of any medicines they took earlier, and
• could at least move and were able to carry out work of a light nature
1382 participants from 41 countries entered this trial.
What Treatment Did the Participants Receive:
ACZ885, was given at a dose of 200 milligrams (mg): one 50 mg injection and
one 150 mg injection under the skin. Both injections were given on Day 1 of the 21-day treatment cycle.
Placebo looks like the trial drug but does not have any trial drug in it. Using a placebo helps researchers better understand the effect of a trial drug.
Researchers randomly assigned participants to the treatment groups using a computer. None of the participants, trial doctors, or trial staff knew what treatment the participants were receiving. Some trials are done this way because knowing what treatment the participants receive can affect the results of the trial. Doing a trial this way helps to make sure that the results are looked at with fairness across all treatments
What Happened During This Trial:
Before Treatment:
1 Month
Trial doctors checked the participants’ health and advanced
NSCLC to make sure they could be in this clinical trial.
During Treatment:
1381 patients were randomly assigned and treated with one of the
following 2 treatments:
ACZ885 200 mg (692 participants)
Placebo (689 participants)
Participants could receive treatment
for up to 18 cycles or until:
• their cancer returned,
• they had severe side effects,
• they started a new treatment,
• they left the trial by their
own will or due to the trial
doctor’s decision, or
• they were unreachable for
further follow up or died
What is a cycle: A cycle is a treatment period of 21 days that can be repeated as needed. The participants received the trial drug once on Day 1 of each cycle.
As the trial was stopped earlier than planned, the treatment was
also stopped earlier. Trial doctors checked the participants' advanced NSCLC and general health throughout the trial.After Treatment-Up to 4 years
Participants’ health was monitored for 4 months after their last dose.
Participants were checked for return of cancer or death until
the end of the trial.
How Long Did Participants Remain Cancer-free after receiving ACZ885 compared to placebo?The time for which the participants remained cancer-free after
receiving ACZ885 was similar to those who received placebo.To answer this question, the researchers monitored how long the participants remained cancer-free since the start of treatment.
Participants remained cancer-free on average for 35 months after receiving ACZ885 compared to 30 months after receiving placebo. As the time for which the participants remained cancer-free was not notably different, researchers concluded that ACZ885 did not increase the amount of time the participants remained cancer-free when compared to placebo.
The average time participants remained cancer-free
ACZ885 200mg -35 months
Placebo-30 months.
What Adverse Events did participants have?
Trial doctors keep track of all adverse
events that happen in trials, even
if they think the adverse events are
not related to the trial treatments.
Many trials are needed to
know if a drug or treatment
causes an adverse event.
This section is a summary of the
adverse events that happened
after the start of the trial treatments
up to 4 months after last dose.
An adverse event is:
• Any sign or symptom that the
participants have during a trial
• Considered serious when it is
life-threatening, causes lasting
problems, the participant needs
hospital care, or results in death
Adverse events may or may not be
caused by treatments in the trial87% (1207 of 1381) of the participants had adverse events. 22% (287 of 1381) participants had adverse events that were considered serious. 26 participants died. The most common cause of death was worsening of the cancer. 65 participants left the trial due to an adverse event. The researchers concluded there were no new safety concerns for ACZ885 for this trial.
How many participants had adverse events
ACZ885 200mg
1 serous adverse event 141 of 692 -20 percent
Had at least 1 other adverse event 465 of 692 67 percent
Stopped treatment due to adverse event 34 of 692 5 percent
Died 9 of 692 1percent.
Placebo 689 participants
1 serous adverse event 146 of 689 -21 percent
Had at least 1 other adverse event 455 of 689 66 percent
Stopped treatment due to adverse event 31 of 689 4 percent
Died 17 of 689 2percent.
What serious events did the participant haveACZ885
COVID 19 48 of 692
Difficulty in breathing 7 of 692
Dyspnea
Lung infection 13 of 692
Pneumonia
Placebo
COVID 19 48 of 692
Difficulty in breathing 2 of 689
Dyspnea
Lung infection 9 of 689
Pneumonia
Other Adverse Events
ACZ885
Back pain 61 of 692 9 percent
Cough 89 of 692 13 percent
Diarrhea 57 of 692 8 percent
Difficulty in breathing 67 of 692 10 percent
Dyspnea
Extreme tiredness 70 of 692 10 percent
Fatigue
Headache 31 of 692 4 percent
Increase in body weight 63 of 692 9 percent
Weight increased
Increase in liver test value of alanine aminotransferase in the blood Alanine aminotransferase 65 of 692 9 percent
increased Joint pain 74 of 692 9 percent
Arthralgia
Placebo 689 participants
Back pain 56 of 689 8 percent
Cough 108 of 689 16 percent
Diarrhea 48 of 689 7 percent
Difficulty in breathing 50 of 689 7 percent
Dyspnea
Extreme tiredness 60 of 689 9 percent
Fatigue
Headache 60 of 689 9 percent
Increase in body weight 48 of 689 7 percent
Weight increased
Increase in liver test value of alanine aminotransferase in the blood Alanine aminotransferase
49 of 689 7 percent
increased Joint pain 88 of 689 13 percent
Arthralgia
What We Learned from this Trial
Researchers learned about the effects of ACZ885 in people with advanced NSCLC.
• The sponsors decided to end the trial early as the initial analysis showed
that ACZ885 did not have the expected effect on participants who had
complete surgical removal of their advanced NSCLC.
The researchers found no significant difference between the effect of
ACZ885 and placebo in treating adults with advanced NSCLC.
• Researchers found no new safety concerns for ACZ885.
At the time of this report no new trials with ACZ885 in advanced NSCLC are planned.
Where can I learn more about this trial?
More information about the results and adverse events in this trial can be found in
the scientific summary of the results available on the Novartis Clinical Trial Results website www.novctrd.com
For more information about this trial, go to any of these websites:
• clinicaltrials.gov – search using the number NCT03447769
• clinicaltrialsregister.eu/ctr-search/search – search using the number
2017‑004011‑39
Full clinical trial title: A phase III, multicenter, randomized, double-blind,placebo-controlled study evaluating the efficacy and safety of canakinumab versus placebo as adjuvant therapy in adult patients with stages American Joint Committee on Cancer (AJCC)/ Union for International Cancer Control (UICC) v. 8 II-IIIA and IIIB (T>5cm N2) completely resected (R0) non-small cell lung cancer (NSCLC)REC name
South Central - Hampshire A Research Ethics Committee
REC reference
18/SC/0015
Date of REC Opinion
21 Feb 2018
REC opinion
Further Information Favourable Opinion