Non-small Cell Lung Cancer Stage INCT03603002
Pathologic and Immunologic Response After Ablative Radiation in Lung Cancer
A study testing Post-SABR Biopsy in people with Non-small Cell Lung Cancer Stage I, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This is a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Non-small Cell Lung Cancer Stage I
- What is being tested?
- Post-SABR Biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2018to 27 Jun 2025
- Phase
- Interventional
- 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
- Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Age > 18 year
- Confirmed non-small cell lung cancer after initial biopsies
- Patient with accessible tumor for biopsy
- Patient is to have sufficient initial core biopsy samples for tissue analyses
- Stage I lung cancer
Show all 10Show fewer
- Adequate normal organ and marrow function
- Patient with tumor amenable to SABR treatment as determined by a radiation oncologist
- Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
Who cannot join
- Primary tumors not amenable to serial core biopsies.
- Prior thoracic radiation in the region that will be treated by SABR.
- Patient may not be receiving any other concurrent investigational agents or chemotherapy.
- Patient may not be receiving or received immunotherapy.
- Patients may not be on or use steroids within 14 days before radiation, and from the duration of radiation to the time of the post-SABR biopsies and blood samples.
- Female patients who are pregnant from screening to completion of SABR
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Studying the Pathologic and Immunologic Response After Ablative Radiation in Stage I Non-Small Cell Lung Cancer
This is a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.
Read the detailed description
Lung cancer is the leading cause of cancer death in the United States. While stereotactic ablative radiotherapy (SABR) is delivered as standard treatment in patients with medically inoperable stage I non-small cell lung cancer (NSCLC), an alarming 30-40% of these patients still develop disease recurrence just outside of the radiation field and deadly distant metastases in their lifetime. Furthermore, since the abscopal response was reported in advanced NSCLC where a systemic cancer response was induced in areas away from the irradiated site when radiation was combined with immunotherapy, multiple clinical trials are currently investigating the role of combining these two modalities. Significantly, how SABR alone increases immunogenicity of a tumor is unknown. There is a critical need to elucidate the mechanism by which SABR alone incites the immune system to better develop future rational combinations of immunotherapy with SABR.
SABR induced cell death will ultimately activate downstream cytotoxic T-cells and cause T-cell influx into the tumor to enhance immunogenic tumor cell kill. This is accomplished with SABR-induced tumor antigen-both mutation-associated neoantigen and tumor-associated antigen- release, priming of downstream cytotoxic T-cells, leading to specific T-cell clonal expansion, and resultant influx of these activated cytotoxic T-cells into the tumor and blood to enhance immune-mediated tumor cell kill.
Herein the investigator proposes a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.
The results of this pilot study may have the potential to translate into improved systemic outcomes for patients with NSCLC through future integrated trials of immune checkpoint blockade antibodies that specifically relieve the immunosuppression on the T-cell population found to be activated by SABR. Clarifying SABR-induced immune changes in the tumor and blood will identify pathways that may be exploited to enhance systemic immunity to kill micro-metastatic disease and mitigate relapse in the next generation of clinical trials.
Additional corollary imaging studies using dual-energy (DE) computed tomography (CT), a novel imaging modality that improves the material decomposition ability of CTs, may identify new imaging markers for post-SABR treatment response by comparing DE-CT imaging characteristics with SABR fields and pathologic response.
- Conditions
- Non-small Cell Lung Cancer Stage I
- Being tested
- Post-SABR Biopsy
- 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.
Post-SABR BiopsyDiagnostic test
Post-SABR Biopsy
| Study group | Role | What they receive |
|---|---|---|
| Stage I NSCLC with SABR Therapy | Experimental | Participants receive stereotactic ablative radiotherapy (SABR) and pre-SABR biopsy as part of standard of care and then receive a post-SABR biopsy after receiving SABR. Receives: Diagnostic Test: Post-SABR Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Examine the T-cell Receptor Profile Changes Induced in the Tumor After SABR
T-cell receptor (TCR) profile changes in the tumor using TCR sequencing.
Measured: Baseline to up to 7 days after SABR treatment
Secondary outcomes (6)
Evaluate Candidate Tumor Antigens Released From the Tumor by SABR
Candidate tumor antigens, mutation associated neo-antigens (MANAs), and tumor associated neo-antigens, (TAAs) released from the tumor by SABR
Measured: post-SABR
Semiquantitative Scoring System to Describe the Influx of Key Tumor Infiltrating Lymphocytes in the Tumor After SABR.
Semiquantitative immunohistochemistry scoring system was used to evaluate pathological changes, immune-cell populations (CD8, FoxP3), within the tumor. Semiquantitative scoring system: 0 None, 1: 1-5, 2: 6-10, 3: 11-20, 4: 21 or more positive cells per high powered field (400x). Score for each participant is reported.
Measured: 5 to 7 day post SABR
Detection of Peripheral Neoantigen-specific T-cell Responses and Dynamics After SABR.
Assessed by the Mutation-Associated Neoantigen Functional Expansion of Specific T-cells (MANAFEST) assay. Number of participants where a peripheral neoantigen-specific T-cell responses and dynamics was detected is reported.
Measured: Within one year after SABR
Iodine Concentration (mg/mL) After SABR Measured With Dual-Energy CT Imaging
Dual-energy (DE) CT imaging characteristics after SABR. Evaluate iodine concentration measurement pre and post SABR treatment relationship using dual-energy (DE) CT imaging.
Measured: Pre-SABR, 5-7 days post-SABR
Number of Participants With Grade 2+ Toxicity Events
Patients with grade 2+ toxicity measured by NCIs Common Terminology Criteria for Adverse Events (CTCAE 4.0), due to post-SABR biopsy.
Measured: Pre-SABR, Post-SABR, 3, 6, 9 and 12 months.
Semiquantitative Scoring System to Describe the Influx of Key Tumor Infiltrating Lymphocytes Within the Peritumoral Stoma After SABR.
Semiquantitative immunohistochemistry scoring system was used to evaluate pathological changes, (CD8, FoxP3, PD-L1/PD-1) expression within the peritumoral stoma after SABR. Semiquantitative scoring system: 0 None, 1: 1-5, 2: 6-10, 3: 11-20, 4: 21 or more positive cells per high powered field (400x). Score for each participant is reported.
Measured: 5 to 7 day post SABR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2018
- Study start16 Oct 2018
- Primary completion1 Sep 2021
- Study completion27 Jun 2025
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 Non-small Cell Lung Cancer Stage IStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Khinh Ranh Voong, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03603002
- Sponsor's protocol ID
- J1826
- Other IDs
- IRB00163415
- Status last verified
- Jun 2026
- First submitted
- 18 Jul 2018
- Last updated
- 2 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studying the Pathologic and Immunologic Response After Ablative Radiation in Stage I Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03603002
- Acronym / sponsor ID
- J1826
- Conditions
- Non-small Cell Lung Cancer Stage I
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- 16 Oct 2018 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 27 Jun 2025 (actual)
- First posted
- 27 Jul 2018 (actual)
- Results
- Posted 26 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.
Detailed description
Lung cancer is the leading cause of cancer death in the United States. While stereotactic ablative radiotherapy (SABR) is delivered as standard treatment in patients with medically inoperable stage I non-small cell lung cancer (NSCLC), an alarming 30-40% of these patients still develop disease recurrence just outside of the radiation field and deadly distant metastases in their lifetime. Furthermore, since the abscopal response was reported in advanced NSCLC where a systemic cancer response was induced in areas away from the irradiated site when radiation was combined with immunotherapy, multiple clinical trials are currently investigating the role of combining these two modalities. Significantly, how SABR alone increases immunogenicity of a tumor is unknown. There is a critical need to elucidate the mechanism by which SABR alone incites the immune system to better develop future rational combinations of immunotherapy with SABR.
SABR induced cell death will ultimately activate downstream cytotoxic T-cells and cause T-cell influx into the tumor to enhance immunogenic tumor cell kill. This is accomplished with SABR-induced tumor antigen-both mutation-associated neoantigen and tumor-associated antigen- release, priming of downstream cytotoxic T-cells, leading to specific T-cell clonal expansion, and resultant influx of these activated cytotoxic T-cells into the tumor and blood to enhance immune-mediated tumor cell kill.
Herein the investigator proposes a pilot study to compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay. This will be coupled with (1) novel genomic analysis of candidate tumor antigens that may be released from the pre-SABR tumor and (2) functional validation assays to screen post-treatment peripheral blood T-cells for reactivity to these released candidate tumor antigens. In addition, cell-based analysis will be used to identify changes in key T-cell infiltrates into the post-SABR tumor.
The results of this pilot study may have the potential to translate into improved systemic outcomes for patients with NSCLC through future integrated trials of immune checkpoint blockade antibodies that specifically relieve the immunosuppression on the T-cell population found to be activated by SABR. Clarifying SABR-induced immune changes in the tumor and blood will identify pathways that may be exploited to enhance systemic immunity to kill micro-metastatic disease and mitigate relapse in the next generation of clinical trials.
Additional corollary imaging studies using dual-energy (DE) computed tomography (CT), a novel imaging modality that improves the material decomposition ability of CTs, may identify new imaging markers for post-SABR treatment response by comparing DE-CT imaging characteristics with SABR fields and pathologic response.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Compare pre- and post-SABR core biopsies of stage I NSCLC tumors to identify SABR-induced immune-mediated tumor recognition based on a significant and specific expansion of T-cell clones using a novel T-cell receptor (TCR) sequencing assay.
| Arm | Type | Receives |
|---|---|---|
| Stage I NSCLC with SABR Therapy | Experimental | Diagnostic Test: Post-SABR BiopsyParticipants receive stereotactic ablative radiotherapy (SABR) and pre-SABR biopsy as part of standard of care and then receive a post-SABR biopsy after receiving SABR. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- Age > 18 year
- Confirmed non-small cell lung cancer after initial biopsies
- Patient with accessible tumor for biopsy
- Patient is to have sufficient initial core biopsy samples for tissue analyses
Key exclusion criteria (6 listed)
- Primary tumors not amenable to serial core biopsies.
- Prior thoracic radiation in the region that will be treated by SABR.
- Patient may not be receiving any other concurrent investigational agents or chemotherapy.
- Patient may not be receiving or received immunotherapy.
- Patients may not be on or use steroids within 14 days before radiation, and from the duration of radiation to the time of the post-SABR biopsies and blood samples.
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 |
|---|---|---|
| Post-SABR BiopsyPost-SABR Biopsy | Diagnostic test | Stage I NSCLC with SABR Therapy |
Primary outcome
Examine the T-cell Receptor Profile Changes Induced in the Tumor After SABR
Time frame: Baseline to up to 7 days after SABR treatment
T-cell receptor (TCR) profile changes in the tumor using TCR sequencing.
6 secondary outcomes
Evaluate Candidate Tumor Antigens Released From the Tumor by SABR
Time frame: post-SABR
Semiquantitative Scoring System to Describe the Influx of Key Tumor Infiltrating Lymphocytes in the Tumor After SABR.
Time frame: 5 to 7 day post SABR
Detection of Peripheral Neoantigen-specific T-cell Responses and Dynamics After SABR.
Time frame: Within one year after SABR
Iodine Concentration (mg/mL) After SABR Measured With Dual-Energy CT Imaging
Time frame: Pre-SABR, 5-7 days post-SABR
Number of Participants With Grade 2+ Toxicity Events
Time frame: Pre-SABR, Post-SABR, 3, 6, 9 and 12 months.
Semiquantitative Scoring System to Describe the Influx of Key Tumor Infiltrating Lymphocytes Within the Peritumoral Stoma After SABR.
Time frame: 5 to 7 day post SABR
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Khinh Ranh Voong, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Post-SABR Biopsy in people with Non-small Cell Lung Cancer Stage I, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 10 inclusion and 6 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: finished, as of the sponsor's last update on 2 Jul 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 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2024). 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?
Examine the T-cell Receptor Profile Changes Induced in the Tumor After SABR (time frame: Baseline to up to 7 days after SABR treatment). 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 2 Jul 2026.