NSCLC Stage IVPhase 2IRRADIATE-LungNCT05691829
Immunotherapy With Non-Ablative Radiation in Previously Untreated Patients With Stage IV NSCLC
A Phase 2 study testing Pembrolizumab, Radiation and Chemotherapy in people with NSCLC Stage IV, run by NYU Langone Health at 1 site in United States.
Trial summary
The purpose of this study is to test if low dose radiation, which is routinely used in treating patients with lung cancer for symptom control, can improve the results from the standard treatment with pembrolizumab and chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- NSCLC Stage IV
- What is being tested?
- Pembrolizumab, Radiation and Chemotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2023to 21 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Histologically documented, metastatic NSCLC with no previous systemic therapy
- At least 2 distinct measurable metastatic sites, which are 1 cm or larger; patients can have radiation to multiple measurable disease sites as clinically indicated, however, there must be at least 1 measurable non-radiated target lesion for response assessment.
- Agreeable to provide archival tissue for correlative studies; if no archival tissue available may obtain an exemption by the study team.
- Be at least 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
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- Have a performance status of ≤1 ECOG Performance Scale.
- Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 10 days of treatment initiation
- Have one measurable lesion of at least 1 cm outside the planned radiation field (defined as not receiving direct beam from any of the treatment portals).
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first 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 must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had prior chemotherapy, immunotherapy or targeted small molecule therapy within 6 months prior to study Day 1.
- Patient who have previously received radiation overlapping, as determined by the treating radiation oncologist, with the current planned radiation treatment fields are ineligible.
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- Patient's treated with whole brain radiation therapy are ineligible.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases (with SRS and/or neurosurgery) may participate provided they are clinically stable and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication.
- Patients who have not recovered (i.e., ≤ Grade 2 or at baseline) from adverse events due to a previously administered agent. *Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has history of autoimmune disorders, (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Patients with prior history of chemoradiation for lung cancer
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Immunotherapy With Non-Ablative Radiation in Previously Untreated Patients With Stage IV NSCLC
The purpose of this study is to test if low dose radiation, which is routinely used in treating patients with lung cancer for symptom control, can improve the results from the standard treatment with pembrolizumab and chemotherapy. In this study, only individuals who have NSCLC that is advanced (Stage IV), or has come back (recurred), will be able to participate.
Read the detailed description
This is a phase II open-label trial of pembrolizumab sequentially following upfront non-ablative focal therapy to up to five distinct metastatic subsites in de novo stage IV Non-Small Cell Lung Cancer (NSCLC). The primary goal of this trial is to evaluate the efficacy defined by time to progression or death with upfront non-ablative focal radiation (RT) to index lesions as a way of enhancing the anti-tumor immune response to pembrolizumab. Adult patients with metastatic NSCLC, with at least 2 measurable lesions and those Patients with metastatic NSCLC who are previously untreated are eligible for the study if they meet all inclusion criteria, and do not satisfy any exclusion criteria. Participants will receive standard of care immunotherapy of Pembrolizumab in addition to non-ablative radiation. The intervention is the low dose fractionation, 4Gy x 5, in the upfront treatment of de novo stage IV NSCLC in up to five distinct subsites of metastatic NSCLC.
- Conditions
- NSCLC Stage IV
- Being tested
- Pembrolizumab, Radiation, Chemotherapy
- Keywords
- Lung, Immunotherapy, Fraction non-ablative radiation, untreated patients, metastatic
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475
Pembrolizumab 200mg solution administered intravenously every 3 weeks for 6 cycles followed by maintenance therapy until progression of disease or unacceptable toxicity (standard of care). Administered alongside chemotherapy.
RadiationRadiation
One-time, up-front radiation delivered at up to five metastatic subsites at a 4 Gy x 5 radiation dose fractionation schedule. Radiation will be delivered within five days before or after initiation of first cycle of pembrolizumab treatment. Radiation modality and technique will be determined at the discretion of the treating radiation oncologist.
ChemotherapyDrug
Administered alongside pembrolizumab every 3 weeks for 6 cycles per institutional standard of care. For non-squamous, the standard chemotherapy option of choice is carboplatin and pemetrexed. For squamous cell carcinoma, the chemotherapy used would be carboplatin and paclitaxel or nab-paclitaxel
| Study group | Role | What they receive |
|---|---|---|
| Untreated Patients With Stage IV NSCLC | Experimental | Participants will receive radiation in concert with starting chemotherapy with pembrolizumab for up to 6 cycles (18 weeks), followed by continued treatment with pembrolizumab (standard of care). Patients will be followed for 1 year following the completion of the core study period of 6 cycles. Receives: Drug: Pembrolizumab; Radiation: Radiation; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by End of Treatment Cycle 4
Defined as the best response recorded from the start of the study treatment until the end of treatment Cycle 4, either Complete Response or Partial Response. A CR is defined as the disappearance of all target lesions (TLs) and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. A PR is defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD.
Measured: Up to Week 12 (End of Cycle 4 - each cycle is 21 days)
Secondary outcomes (3)
Progression-Free Survival (PFS) at Final Follow-Up
PFS is defined as the time from initiation of study drug post-radiation, until the first documented, confirmed progression of disease or death.
Measured: From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks
Overall Survival (OS) at Final Follow-Up
OS is defined as the time (in weeks) to death from the start of drug therapy.
Measured: From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks
Percentage of Participants With an Objective Response
An objective response (Complete Response or Partial Response) is defined as lasting continuously for 6 months and starting any time within 12 months of initiating therapy. A CR is defined as the disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. A PR is defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2023
- Study start24 Jan 2023
- Primary completion20 Jun 2024
- Study completion21 Apr 2025
Why it stopped: Terminated due to insufficient enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NSCLC Stage IVStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vamsidhar Velcheti, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05691829
- Sponsor's protocol ID
- 22-00673
- Acronym
- IRRADIATE-Lung
- Status last verified
- Jul 2025
- First submitted
- 11 Jan 2023
- Last updated
- 29 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Vamsidhar.Velcheti@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Immunotherapy With Non-Ablative Radiation in Previously Untreated Patients With Stage IV NSCLC
- ClinicalTrials.gov ID
- NCT05691829
- Acronym / sponsor ID
- IRRADIATE-Lung / 22-00673
- Conditions
- NSCLC Stage IV
- Keywords
- Lung, Immunotherapy, Fraction non-ablative radiation, untreated patients, metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to insufficient enrollment.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 24 Jan 2023 (actual)
- Primary completion
- 20 Jun 2024 (actual)
- Study completion
- 21 Apr 2025 (actual)
- First posted
- 20 Jan 2023 (actual)
- Results
- Posted 29 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test if low dose radiation, which is routinely used in treating patients with lung cancer for symptom control, can improve the results from the standard treatment with pembrolizumab and chemotherapy. In this study, only individuals who have NSCLC that is advanced (Stage IV), or has come back (recurred), will be able to participate.
Detailed description
This is a phase II open-label trial of pembrolizumab sequentially following upfront non-ablative focal therapy to up to five distinct metastatic subsites in de novo stage IV Non-Small Cell Lung Cancer (NSCLC). The primary goal of this trial is to evaluate the efficacy defined by time to progression or death with upfront non-ablative focal radiation (RT) to index lesions as a way of enhancing the anti-tumor immune response to pembrolizumab. Adult patients with metastatic NSCLC, with at least 2 measurable lesions and those Patients with metastatic NSCLC who are previously untreated are eligible for the study if they meet all inclusion criteria, and do not satisfy any exclusion criteria. Participants will receive standard of care immunotherapy of Pembrolizumab in addition to non-ablative radiation. The intervention is the low dose fractionation, 4Gy x 5, in the upfront treatment of de novo stage IV NSCLC in up to five distinct subsites of metastatic NSCLC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Untreated Patients With Stage IV NSCLC | Experimental | Drug: Pembrolizumab, Radiation: Radiation, Drug: ChemotherapyParticipants will receive radiation in concert with starting chemotherapy with pembrolizumab for up to 6 cycles (18 weeks), followed by continued treatment with pembrolizumab (standard of care). Patients will be followed for 1 year following the completion of the core study period of 6 cycles. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Histologically documented, metastatic NSCLC with no previous systemic therapy
- At least 2 distinct measurable metastatic sites, which are 1 cm or larger; patients can have radiation to multiple measurable disease sites as clinically indicated, however, there must be at least 1 measurable non-radiated target lesion for response assessment.
- Agreeable to provide archival tissue for correlative studies; if no archival tissue available may obtain an exemption by the study team.
- Be at least 18 years of age on day of signing informed consent.
Key exclusion criteria (19 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had prior chemotherapy, immunotherapy or targeted small molecule therapy within 6 months prior to study Day 1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475Pembrolizumab 200mg solution administered intravenously every 3 weeks for 6 cycles followed by maintenance therapy until progression of disease or unacceptable toxicity (standard of care). Administered alongside chemotherapy. | Drug | Untreated Patients With Stage IV NSCLC |
| RadiationOne-time, up-front radiation delivered at up to five metastatic subsites at a 4 Gy x 5 radiation dose fractionation schedule. Radiation will be delivered within five days before or after initiation of first cycle of pembrolizumab treatment. Radiation modality and technique will be determined at the discretion of the treating radiation oncologist. | Radiation | Untreated Patients With Stage IV NSCLC |
| ChemotherapyAdministered alongside pembrolizumab every 3 weeks for 6 cycles per institutional standard of care. For non-squamous, the standard chemotherapy option of choice is carboplatin and pemetrexed. For squamous cell carcinoma, the chemotherapy used would be carboplatin and paclitaxel or nab-paclitaxel | Drug | Untreated Patients With Stage IV NSCLC |
Primary outcome
Percent of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by End of Treatment Cycle 4
Time frame: Up to Week 12 (End of Cycle 4 - each cycle is 21 days)
Defined as the best response recorded from the start of the study treatment until the end of treatment Cycle 4, either Complete Response or Partial Response. A CR is defined as the disappearance of all target lesions (TLs) and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. A PR is defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD.
3 secondary outcomes
Progression-Free Survival (PFS) at Final Follow-Up
Time frame: From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks
Overall Survival (OS) at Final Follow-Up
Time frame: From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks
Percentage of Participants With an Objective Response
Time frame: Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Vamsidhar.Velcheti@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Vamsidhar Velcheti principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Radiation and Chemotherapy in people with NSCLC Stage IV, run by NYU Langone Health at 1 site in United States.
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 12 inclusion and 19 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: stopped early, as of the sponsor's last update on 29 Jul 2025. 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 United States. 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?
Yes. Results are posted in the registry (first posted 29 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by End of Treatment Cycle 4 (time frame: Up to Week 12 (End of Cycle 4 - each cycle is 21 days)). 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 29 Jul 2025.