Pathologic and Immunologic Response After Ablative Radiation in Lung Cancer

September 24, 2025 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Bayview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Stage I NSCLC with SABR Therapy
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.
Diagnostic test: Post-SABR Biopsy
Post-SABR Biopsy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline to up to 7 days after SABR treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Evaluate Candidate Tumor Antigens Released From the Tumor by SABR
Time Frame: post-SABR
Candidate tumor antigens, mutation associated neo-antigens (MANAs), and tumor associated neo-antigens, (TAAs) released from the tumor by SABR
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
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.
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
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.
Within one year after SABR
Dual-energy (DE) CT Imaging Characteristics After SABR
Time Frame: 1 year
Dual-energy (DE) CT imaging characteristics after SABR. Evaluate relationship between dual-energy (DE) CT imaging characteristics, radiation dose, and early post-SABR pathologic outcomes after treatment with SABR.
1 year
Number of Participants With Grade 2+ Toxicity Events
Time Frame: Pre-SABR, Post-SABR, 3, 6, 9 and 12 months.
Patients with grade 2+ toxicity measured by NCIs Common Terminology Criteria for Adverse Events (CTCAE 4.0), due to post-SABR biopsy.
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
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.
5 to 7 day post SABR

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Khinh Ranh Voong, MD, Johns Hopkins University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 16, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 27, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 27, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 14, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 24, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • J1826
  • IRB00163415 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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