PACIFIC 6
Research type
Research Study
Full title
A Phase II, Open-Label, Multi-Centre, International Safety Study of Durvalumab Following Sequential Chemotherapy and Radiation Therapy in Patients with Stage III, Unresectable Non-Small Cell Lung Cancer (PACIFIC 6)
IRAS ID
252902
Contact name
Holly Spencer
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2018-002220-16
Duration of Study in the UK
3 years, 7 months, 0 days
Research summary
Lung cancer has been the most common cancer in the world for several decades. By 2012, there were an estimated 1.8 million new cases, representing 12.9% of all new cancers. Non-small cell lung cancer represents approximately 80% to 85% of all lung cancers. Until recently Chemotherapy and radiation therapy was the main treatment option for people with locally advanced non-small cell lung cancer that is confined to the lung.
Researchers have found that sometimes the body’s own immune system may slow down or prevent cancer growth. Sometimes though, this natural immune system response stops working, and the cancer is not killed by your own immune system. Research has shown that in some participant’s, cancer cells and immune cells start to express signals that stop the body’s immune system from killing the cancer. One such signal is called Programmed Cell Death Ligand 1, or PD-L1 for short.
Durvalumab is a new medicine that blocks the PD-L1 signal. Durvalumab was recently approved by the European Commission as a treatment for patients with lung cancer that cannot be surgically removed and expresses PD-L1, after the completion of chemotherapy and radiation therapy. Durvalumab has also been approved as a treatment for same type of lung cancer by the United States (US) Food and Drug Administration (FDA).
so far the evidence showing a benefit for durvalumab comes from patients treated with chemotherapy and radiotherapy administered at the same time (so called concurrent chemoradiotherapy
The purpose of this study is to determine whether durvalumab is safe and tolerated in patients with non-small cell lung cancer after completion of treatment with chemotherapy followed by radiation therapy. he study will
also assess whether the administration of durvalumab after chemotherapy and radiotherapy is safe and slows the growth of the cancer.This research study is planned to go on for approximately 4 years and will include around 150 participants with lung cancer which cannot be surgically removed from about 6 countries.
The study sponsor is AstraZeneca AB.
LAY SUMMARY OF STUDY RESULTS:
The participants in this trial received durvalumab.
The main questions the researchers wanted to answer in this trial were:
• What severe medical problems did the doctors report as possibly related to durvalumab?
• How long did the participants live during this trial?
• How long did the participants live during this trial without their cancer growing or spreading?
There were 4.3% of participants who had severe (grade 3 and 4) medical problems during their first 6 months in the trial that the trial doctors reported as possibly being related to durvalumab. This was 5 out of 117 participants. Overall, the participants lived for a median of 39.0 months during this trial. The median is the time at which 50.0% of the participants are still alive during this trial. Overall, 50.0% of the participants lived for 13.1 months or longer during this trial without their cancer growing or spreading. There were 76.9% of participants who had medical problems that the trial doctors reported as possibly being related to the trial treatment. This was 90 out of 117 participants. The researchers asked for the help of people with locally advanced non-small cell lung cancer (NSCLC). The participants in this trial were 39 to 85 years old when they joined. All the participants had already received a type of treatment called sequential chemoradiotherapy (sCRT) for their locally advanced NSCLC. sCRT is a treatment where people receive radiation therapy after completing their chemotherapy treatment. This trial included 117 participants, including 73 males and 44 females in 6 countries:
Country Number of participants
France 16
Germany 18
Italy 39
Spain 30
UK 12
US 2The participants in this trial received durvalumab. The doses of durvalumab were measured in milligrams (mg). This was an “open-label” trial. This means the participants, researchers, trial doctors, and other trial staff knew what each participant was receiving: Durvalumab; 117 participants; 1,500 mg doses of durvalumab through a needle directly into a vein over a period of time (IV infusion). Once every 4 weeks for up to 2 years.
The participants were in the trial for about 2 years and 3 months, but the entire trial took 4 years to finish. The trial started in April 2019 and ended in April 2023.
This is a summary of the main results from this trial overall. The individual results of each participant might be different and are not in this summary.
Researchers kept track of the severe medical problems that the participants had during their first 6 months in this trial that the doctors reported as possibly related to durvalumab. These medical problems are called severe adverse reactions. All adverse reactions were graded by the researchers on a scale from 1 to 5. In this trial, an adverse reaction was considered “severe” if it was grade 3 or 4.Grade Meaning
1 Mild, likely does not interfere with daily life
2 Moderate, may interfere with daily life
3 Severe, likely does interfere with daily life or
requires hospitalization
4 Life-threatening, requires immediate care
5 Causes deathThe table below lists the severe adverse reactions that happened during the participants’ first 6 months in this trial.
Severe Adverse Reactions
Durvalumab
(out of 117 participants)Inflammation of the lung tissue (Pneumonitis) 1.7% (2)
A low number of a type of white blood cells called
leukocytes 0.9% (1)
Not enough of certain hormones being made by
the body (Adrenal insufficiency) 0.9% (1)
Underactive thyroid, which is a gland in the neck
(Hypothyroidism) 0.9% (1)Researchers kept track of how long the participants lived during the trial after starting trial treatment. The researchers looked specifically at 2 measurements called the median overall survival and the overall survival rate. The median overall survival is the time when 50.0% of the participants were still alive during the trial. The results for median overall survival are for Durvalumab (117 participants): 39.0 months.
The overall survival rate is the percentage of participants who were alive at specific time points after starting trial treatment. The results for the overall survival rates at one year are for Durvalumab (117 participants): 83.5%. Overall survival rate at 2 years was 67.2%. Overall survival rate at 3 years was 56.5%.
Researchers kept track of how long the participants lived during the trial without their cancer growing or spreading. The researchers looked specifically at 2 measurements called the median progression-free survival and the progression-free survival rate. The median progression-free survival is the time when 50.0% of the participants were still alive without their cancer growing or spreading during the trial. The results for median progression-free survival are for Durvalumab (117 participants): 13.1 months The progression-free survival rate is the percentage of participants who were living without their cancer growing or spreading at specific time points after starting trial treatment. The results for the progression-free survival rates after 1 year are for Durvalumab (117 participants): 50.6% and after 2 year: 35.3%.
This section is a summary of the medical problems that the participants had during this entire trial that the doctors reported as possibly related to the trial treatment. These medical problems are called “adverse reactions”. Earlier in this summary, there was information about the severe adverse reactions from the participants’ first 6 months in the trial. This section of the summary contains information on all the adverse reactions that happened during the entire trial. The serious adverse reactions below happened over the entire trial.
There were 76.9% of participants who had adverse reactions in this trial. This was 90 out of 117 participants. 6.0% (7) participants had serious adverse reactions. 16.2% (19) participants stopped receiving trial treatment due to adverse reactions. The most common serious adverse reaction was inflammation of the lung tissue (Pneumonitis); 4.3% (5). Also a type of lung infection called pneumonia occurred in 0.9% (1) of the participants. Possibly life-threatening scarring and inflammation in the lungs (Interstitial lung disease) occurred in 0.9% (1) of the participants. There was 1 participant who received durvalumab who died because of a serious adverse reaction. This serious adverse reaction was inflammation of the lung tissue (Pneumonitis).
The most common adverse reaction was inflammation of the lung tissue (Pneumonitis). The adverse reactions below happened in 5.0% or more of participants. There were other adverse reactions, but each of those happened in fewer participants occurred in of the participants.
Adverse event Durvalumab (out of 117 participants
Inflammation of the lung tissue (Pneumonitis) 17.1% (20)
Feeling weak or lacking energy (Asthenia) 16.2% (19)
Itchy skin (Pruritus) 14.5% (17)
Underactive thyroid, which is a gland in the neck (Hypothyroidism) 13.7% (16)
Feeling tired (Fatigue) 12.0% (14)Rash 11.1% (13)
Diarrhea 10.3% (12)
Joint pain (Arthralgia) 9.4% (11)
Overactive thyroid, which is a gland
in the neck (Hyperthyroidism) 7.7% (9)
Shortness of breath (Dyspnea) 6.0% (7)REC name
East of England - Essex Research Ethics Committee
REC reference
18/EE/0394
Date of REC Opinion
1 Feb 2019
REC opinion
Further Information Favourable Opinion