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AzTrials

Carcinoma, Non-Small-Cell LungPhase 2RAD-IONCT05401786

Anti-PD-1 Re-challenge After Immune Priming by Ipilimumab and Immune Boosting by Radiotherapy in Advanced NSCLC

A Phase 2 study testing Ipilimumab, Cemiplimab and SBRT in people with Carcinoma, Non-Small-Cell Lung, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Still many advanced non-small cell lung cancer (NSCLC) patients do not benefit from PD-(L)1 inhibition or will eventually develop progression through secondary resistance. Inhibition of CTLA-4, application of radiotherapy together with PD-1 inhibition showed synergistic effects and is deemed safe. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Ipilimumab, Cemiplimab and SBRT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteNetherlands
Study dates
3 Jan 2023to Jun 2026
Phase
Phase 2
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

Who may be able to join

  • Have proven diagnosis of recurrent advanced NSCLC, irrespective of histological subtype.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Must still have measurable disease based on RECIST 1.1 after application of study SBRT. Lesions that were irradiated prior to the study, but have progressed since irradiation but prior to study inclusion will be allowed as measurable disease.
  • Must provide newly obtained tissue from a core or excisional biopsy of a tumor lesion and are willing to have a second biopsy performed from any non-irradiated lesion after the radiation and immune-modulating treatment. This lesion may be used for RECIST measurements.
  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Stage IV NSCLC treated with at least PD-(L)1 blockade. There is no maximum number of previous lines of systemic treatment. Patients with both primary or acquired resistance to PD-(L)1 inhibition may be considered eligible. However, in the 1st stage ≥4 of 12 patients, in the 2nd stage a total of ≥8 of 25 patients and in the 3rd stage a total of ≥27 of 54 patients need to fulfill the definition of acquired resistance. Also, a maximum of 27 patients with a PD-L1 negative tumor will be included.
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  • Have at least 2 separate (metastatic) lesions of which one is eligible for irradiation and another for biopsy and RECIST tumor evaluation.
  • Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
  • Female subject of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the 1st dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the 1st dose of study therapy through 6 months after the last dose of study therapy

Who cannot join

  • The subject must be excluded from participating in the trial if the subject:
  • Has a non-smoking-related targetable driver mutation, e.g. EGFR, ALK, RET or ROS1. Patients with advanced NSCLC with a smoking-related targetable driver mutation, e.g. KRAS or BRAF, may be found eligible if they have a history of ≥10 PY, but only when all options for targeted therapy have been exhausted and when progression on previous PD-(L)1 blockade has occurred.
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the 1st dose of treatment.
  • Has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: Patients who experienced significant autoimmune side effects related to previous PD-(L)1 checkpoint inhibition, i.e. requiring use of steroids or other anti-inflammatory drugs and/or the need to (temporarily) withhold PD-(L)1 checkpoint inhibition, may be considered eligible after discussion with the coordinating investigator if adverse events have recovered, i.e. ≤ Grade 1 or at baseline.
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  • Note: If subjects received major surgery (defined as surgical intervention requiring general or spinal anesthesia and hospital admission), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Major surgery within 14 days prior to start of study treatment is not allowed.
  • Has had previous radical radiation to any tumor site within 3 months prior to study Day 1. Previous palliative radiation to any tumor site is not considered an exclusion criterion; however, this site will not be eligible for SBRT, biopsy location or RECIST tumor evaluation within this study.
  • Has received prior therapy with any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways other than PD-(L)1 blockade, e.g. anti-CD137 or a CTLA-4 antibody.
  • Patients who have uncontrolled central nervous system (CNS) metastases. Patients who have untreated asymptomatic CNS metastases no greater than 2cm before start of treatment may be eligible. Patients who have any CNS lesion that is symptomatic, greater than 2cm, show significant surrounding edema on MRI scan or have leptomeningeal disease will not be eligible. Patients who have previously been treated for CNS metastases are eligible when they comply with the hereby mentioned criteria.
  • NB. A brain lesion is not amendable for study SBRT.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has an active autoimmune disease or a documented history of clinically severe autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Subjects who require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with an active or history of autoimmune disease or syndrome who underwent previous PD-(L)1 checkpoint inhibition without significant side effects, i.e. not requiring use of steroids or other anti-inflammatory drugs and/or the need to (temporarily) withhold PD-(L)1 checkpoint inhibition, may be considered eligible for this trial after discussion with the coordinating investigator. Requirement for immunosuppressive doses of systemic corticosteroids ≤10 mg/day prednisone or equivalent may be considered eligible after discussion as well.
  • Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoek - Netherlands Cancer Institute

    Amsterdam, North Holland, 1066 CX

Other trials in Netherlands

About this study

Still many advanced non-small cell lung cancer (NSCLC) patients do not benefit from PD-(L)1 inhibition or will eventually develop progression through secondary resistance. Inhibition of CTLA-4, application of radiotherapy together with PD-1 inhibition showed synergistic effects and is deemed safe.

Read the detailed description

Still many advanced non-small cell lung cancer (NSCLC) patients do not benefit from PD-(L)1 inhibition or will eventually develop progression through secondary resistance. The aim of this study is to investigate whether the combining of T cell priming by CTLA-4 inhibition (ipilimumab) ad subsequent immune boosting by stereotactic body radiotherapy (SBRT) on 1-4 tumor lesions can re-invigorate the response on PD-1 inhibition (cemiplimab) after initial non-response or secondary resistance to anti-PD-(L)1 treatment. Elaborate translational research by repeat biopsies in combination with blood collection during the different stages of treatment will help improve understanding of the joint effort of these different interventions.

Being tested
Ipilimumab, Cemiplimab, SBRT
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 groups in NCT05401786
Study groupRoleWhat they receive
Anti-CTLA-4, SBRT and PD1ExperimentalParticipants will receive 1 dose of ipilimumab (1mg/kg intravenously) on day 1. After 1 week the participants will receive SBRT (3x8Gy) on at least 1 but no more than 4 tumor lesions. Within 1 week of the last radiation fraction participants will start with cemiplimab (350mg intravenously every 3 weeks) until disease progression, unacceptable toxicity, patient request for discontinuation, or up to 2 years of treatment
Receives: Drug: Ipilimumab; Drug: Cemiplimab; Radiation: SBRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Benefit Rate

    Number of participants with complete response or partial response within the first 6 months or stable disease lasting for minimum 6 months

    Measured: Through study completion, an average of 1 year

Secondary outcomes (6)

  1. Objective Response Rate

    Number of participants with complete response or partial response

    Measured: 12 weeks after re-introduction of PD-1 inhibition (day 1 of week 15)

  2. Disease Control Rate

    Number of participants with complete response, partial response, or stable disease

    Measured: 12 weeks after re-introduction of PD-1 inhibition (day 1 of week 15)

  3. Best overall response

    Best overall response at any time point

    Measured: Through study completion, an average of 1 year

  4. Progression Free Survival

    Time between start of treatment and progressive disease or death

    Measured: From date of start of treatment until first documented progression or the date of death assessed up to 100 months

  5. Overall Survival

    Time between start of treatment and death

    Measured: From date of start of treatment until the date of death assessed up to 100 months

  6. Safety of the study procedure

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: Up to 90 days after last study drug intake

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jun 2022
  2. Study start3 Jan 2023
  3. Primary completion15 Nov 2024
  4. Study completionJun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05401786
Sponsor's protocol ID
M21RAD
Acronym
RAD-IO
Status last verified
Mar 2026
First submitted
17 May 2022
Last updated
12 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab, Cemiplimab and SBRT in people with Carcinoma, Non-Small-Cell Lung, run by The Netherlands Cancer Institute 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 11 inclusion and 15 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 12 Mar 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Clinical Benefit Rate (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05401786.

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 12 Mar 2026.

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