Carcinoma, Non-Small-Cell LungIPON-1NCT04432142
Immune Profiling of Stage III Non-small Cell Lung Cancer Patients Treated With Concurrent Chemoradiation and Adjuvant Durvalumab: A Prospective Observational Phase II Trial
An observational study of Carcinoma, Non-Small-Cell Lung, run by Maastricht Radiation Oncology at 1 site in Netherlands.
Trial summary
Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC (non-small cell lung cancer) patients. Identifying the effect of the treatment on immune cells and what their functional consequences are is an essential first step to come to prognostic and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- How many people
- 45 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Apr 2021to 1 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with stage III NSCLC who are eligible for curative intent concurrent chemotherapy and radiotherapy will be enrolled in the study. They receive standard radiotherapy (60 Gy in 30 fractions of 2 Gy) with protons or photons according to the standard of care. Eligible patients will thereafter receive standard durvalumab immune therapy for 12 months. Eligibility criteria for this study are therefore similar to those for standard of care treatment.
Who may be able to join
- Pathological diagnosis of adequately staged (according to standard practice using chest-CT, FDG-PET, brain imaging MRI/CT) NSCLC
- Participant is willing and able to give informed consent for participation in the trial
- Male or female, aged 18 years or above
- Scheduled to receive one of the following two therapeutic strategies:
- Concurrent chemotherapy and radiotherapy with photons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
- Concurrent chemotherapy and radiotherapy with protons (60 Gy in 30 fractions of 2 Gy) in patients with stage III NSCLC
- Is able and willing to comply with all trial requirement
Who cannot join
- Mixed non-small cell lung cancer with other histologies such as small cell lung cancer
- Not able to comply with the study protocol
- Less than 18 years' old
- Pregnancy or not able to comply with adequate contraception in women with child baring potential
- Previous radiotherapy to the chest for benign or malignant conditions, including radiation for breast cancer
- Previous malignancy treated with chemotherapy, immune therapy or radiotherapy (irrespective of when this happened)
- Previous malignancies treated with surgery only are allowed if 2 years or more before inclusion in the present study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht Radiation Oncology (MAASTRO clinic)
Maastricht, 6229 ET
About this study
Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC (non-small cell lung cancer) patients. Identifying the effect of the treatment on immune cells and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.
Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.
This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.
Read the detailed description
Even with the addition of durvalumab to concurrent chemoradiation, approximately only half of the patients are alive at 3 years, and more have progressed already, either locally or distant. Not much is known regarding to identification of patients that will benefit from adjuvant durvalumab, or regarding resistance to adjuvant durvalumab after chemoradiation. Most data on immunotherapy resistance come from metastatic patients treated with monotherapy PD-(L)1 antagonists. Depending on PD-L1 expression level, 10-44% of patients respond well to PD-(L)1 antagonists. The majority of patients are either unresponsive, or experience a tumor recurrence after achieving an initial response. The development of individual immunological treatment strategies (e.g. selection of best treatment: mono- or combination ICI, ICI combined with chemotherapy, or the addition of radiotherapy) is hampered by the lack of knowledge in the best timing, sequencing, and dosing of all modalities and the lack of optimal biomarkers for monitoring the treatment response. This highlights the need of clear biomarkers that can be used to select the best treatment for each individual patient and predict whether patients will benefit from adjuvant immunotherapy. Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC patients. Identifying the effect of the treatment on immune cells (e.g. T-, B-, NK-cells, dendritic cells, macrophages) and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.
Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.
This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Proton | Patients receiving proton therapy | |
| Photon | Patients receiving photon therapy in 4 fractions or less |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune changes
Number of patients with immune changes in stage III NSCLC patients receiving concurrent chemoradiation with protons or photons followed by durvalumab.
Measured: 3 months
Secondary outcomes (15)
PFS
Progression Free Survival
Measured: 12 months
OS
Overall survival
Measured: 12 months
Toxicity chemoradition
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during and after concurrent chemoradiation, also in relation to the irradiated bone marrow volume
Measured: until 3 months after chemo/radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during courses of Durvalumab
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 of durvalumab and chemoradiation treatment
Measured: Until 12 months after chemo/radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Incidence and severity of adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 and patient reported outcome (PRO)-CTCAE)
Measured: Until 12 months after chemoradiation
Immune changes compared
Number of patients with immune changes that are distinct for proton therapy compared with photon therapy
Measured: Until 12 months after chemoradiation
Cardiac function
Troponins
Measured: Until 12 months after chemoradiation
Cardiac function
ECG QT Interval
Measured: Until 12 months after chemoradiation
Cardiac function
blood pressure
Measured: Until 12 months after chemoradiation
Cardiac function
BNP
Measured: Until 12 months after chemoradiation
Neurocognitive function test
MOS
Measured: Until 12 months after chemoradiation
Neurocognitive function test
Controlled oral word association
Measured: Until 12 months after chemoradiation
Neurocognitive function test
Trail making test
Measured: Until 12 months after chemoradiation
Neurocognitive function test
HVALT-R test
Measured: Until 12 months after chemoradiation
Tumor material
Obtaining tumor material from standard diagnostic material for translational purposes
Measured: Until 12 months after chemoradiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start1 Apr 2021
- Primary completion1 Jul 2024
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht Radiation Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dirk De Ruysscher, MD, PhD, Principal investigator, Maastro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04432142
- Sponsor's protocol ID
- IPON-1
- Acronym
- IPON-1
- Status last verified
- Jan 2026
- First submitted
- 9 Jun 2020
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Profiling of Stage III Non-small Cell Lung Cancer Patients Treated With Concurrent Chemoradiation and Adjuvant Durvalumab: A Prospective Observational Phase II Trial
- ClinicalTrials.gov ID
- NCT04432142
- Acronym / sponsor ID
- IPON-1 / IPON-1
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Maastricht Radiation OncologyUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 16 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC (non-small cell lung cancer) patients. Identifying the effect of the treatment on immune cells and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.
Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.
This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.
Detailed description
Even with the addition of durvalumab to concurrent chemoradiation, approximately only half of the patients are alive at 3 years, and more have progressed already, either locally or distant. Not much is known regarding to identification of patients that will benefit from adjuvant durvalumab, or regarding resistance to adjuvant durvalumab after chemoradiation. Most data on immunotherapy resistance come from metastatic patients treated with monotherapy PD-(L)1 antagonists. Depending on PD-L1 expression level, 10-44% of patients respond well to PD-(L)1 antagonists. The majority of patients are either unresponsive, or experience a tumor recurrence after achieving an initial response. The development of individual immunological treatment strategies (e.g. selection of best treatment: mono- or combination ICI, ICI combined with chemotherapy, or the addition of radiotherapy) is hampered by the lack of knowledge in the best timing, sequencing, and dosing of all modalities and the lack of optimal biomarkers for monitoring the treatment response. This highlights the need of clear biomarkers that can be used to select the best treatment for each individual patient and predict whether patients will benefit from adjuvant immunotherapy. Currently, there is only limited data available on the functional immune changes after concurrent chemoradiation in NSCLC patients. Identifying the effect of the treatment on immune cells (e.g. T-, B-, NK-cells, dendritic cells, macrophages) and what their functional consequences are is an essential first step to come to prognostic and predictive biomarkers.
Many studies investigating the role of immunomodulatory effects of treatment are carried out in either in vitro or in vivo animal models. However, identified factors frequently hamper clinical validation. In addition, as mentioned earlier, although several immunogenic factors have been shown to be released by irradiated tumor cells, so far, only a limited number of studies searched for potential predictive and prognostic immunological biomarkers.
This will be the first time that the immune effects of both treatment modalities will be studied, with, in addition, the immune changes during durvalumab treatment, which are also unknown at present. By getting more insight in the treatment-induced immunomodulatory effects, ultimately, in subsequent projects, this will allow to determine optimal immune stimulation and hence improved outcomes of subsequent durvalumab immune therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Proton | – | –Patients receiving proton therapy |
| Photon | – | –Patients receiving photon therapy in 4 fractions or less |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with stage III NSCLC who are eligible for curative intent concurrent chemotherapy and radiotherapy will be enrolled in the study. They receive standard radiotherapy (60 Gy in 30 fractions of 2 Gy) with protons or photons according to the standard of care. Eligible patients will thereafter receive standard durvalumab immune therapy for 12 months. Eligibility criteria for this study are therefore similar to those for standard of care treatment.
Key inclusion criteria (7 listed)
- Pathological diagnosis of adequately staged (according to standard practice using chest-CT, FDG-PET, brain imaging MRI/CT) NSCLC
- Participant is willing and able to give informed consent for participation in the trial
- Male or female, aged 18 years or above
- Scheduled to receive one of the following two therapeutic strategies:
- Is able and willing to comply with all trial requirement
Key exclusion criteria (7 listed)
- Mixed non-small cell lung cancer with other histologies such as small cell lung cancer
- Not able to comply with the study protocol
- Less than 18 years' old
- Pregnancy or not able to comply with adequate contraception in women with child baring potential
- Previous radiotherapy to the chest for benign or malignant conditions, including radiation for breast cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Immune changes
Time frame: 3 months
Number of patients with immune changes in stage III NSCLC patients receiving concurrent chemoradiation with protons or photons followed by durvalumab.
15 secondary outcomes
PFS
Time frame: 12 months
OS
Time frame: 12 months
Toxicity chemoradition
Time frame: until 3 months after chemo/radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 during courses of Durvalumab
Time frame: Until 12 months after chemo/radiotherapy
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Until 12 months after chemoradiation
Immune changes compared
Time frame: Until 12 months after chemoradiation
Cardiac function
Time frame: Until 12 months after chemoradiation
Cardiac function
Time frame: Until 12 months after chemoradiation
Cardiac function
Time frame: Until 12 months after chemoradiation
Cardiac function
Time frame: Until 12 months after chemoradiation
Neurocognitive function test
Time frame: Until 12 months after chemoradiation
Neurocognitive function test
Time frame: Until 12 months after chemoradiation
Neurocognitive function test
Time frame: Until 12 months after chemoradiation
Neurocognitive function test
Time frame: Until 12 months after chemoradiation
Tumor material
Time frame: Until 12 months after chemoradiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dirk De Ruysscher, MD, PhD principal investigator
Maastro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carcinoma, Non-Small-Cell Lung, run by Maastricht Radiation Oncology at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune changes (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.