NSCLCNCT04146064
Breathomics as Predictive Biomarker for Checkpoint Inhibitor Response
An observational study of NSCLC and Melanoma, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Immunotherapy with agents stimulating the immune system to act against cancer are now a new standard of care in various cancers as lung cancer and melanoma, but also bladder cancer, kidney cancer and head \& neck cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Melanoma, Kidney Cancer
- What is being tested?
- Breathprint analysis and patient-reported outcomes
- How many people
- 190 participants
- Where
- 1 siteCanada
- Study dates
- 24 Feb 2020to 9 Feb 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
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: Subjects included in this study are patients over the age of 18 years with a histologically-confirmed diagnosis of non-small cell lung cancer, melanoma or other solid tumor for which ICI-treatment is a standard of care. Patients must have advanced/metastatic disease and planning to receive ICI treatment (categories defined above) or chemotherapy treatment (cohort 4) at the Princess Margaret Cancer Centre/University Health Network. Study subjects will be consented specifically for that study.
Who may be able to join
- Patients 18 years of age or older
- Histologically confirmed advanced/metastatic non-small cell lung cancer, melanoma or solid tumor such as urothelial, kidney or head and neck cancer and planned treatment with
- NSCLC validation cohort: Pembrolizumab or Nivolumab
- NSCLC Cohort 1: Pembrolizumab-chemotherapy combination therapy 1L
- Melanoma Cohort 2: Nivolumab/ipilimumab combination treatment 1L, Pembrolizumab or nivolumab monotherapy treatment 1L , Ipilimumab
- Solid tumors Cohort 3: Any ICI-treatment, any line
Show all 9Show fewer
- NSCLC Cohort 4: Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy)
- At least one measurable lesion as defined by RECIST 1.1. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
- Able to provide informed consent.
Who cannot join
- Patients who are unable to perform the breathing manoeuvres needed for eNose-analysis of exhaled air.
- Patients who are unable to independently consent to participation in the trial.
- Patients with severe, acute, or chronic medical conditions (including uncontrolled diabetes mellitus) or psychiatric conditions or laboratory abnormalities that in the opinion of the Investigator or their physician may cause undue harm or inconvenience to the patient, or that may interfere with the interpretation of study results.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Breathomics as a Non-invasive, Inexpensive, Point-of-care Predictive Test for Immune Checkpoint Inhibitor Efficacy
Immunotherapy with agents stimulating the immune system to act against cancer are now a new standard of care in various cancers as lung cancer and melanoma, but also bladder cancer, kidney cancer and head \& neck cancer. However, even though a subset of patients derives long-term benefit from these agents, depending of cancer type still at least half of patients do not respond to these new drugs. Our understanding of possible factors predicting whether a patient might actually benefit from immunotherapy is poor. Volatile organic compounds (VOCs) are gases exhaled with a person's breath, which are released into the lung from blood and bacteria and therefore can give information about infections as well as inflammation and possibly cancer cells in a person's body. Breath analysis of these VOCs with special devices called electronic noses (eNose) generate a specific electric signals patterns called breathprints. There is early evidence that specific breathprints can actually help to select patients who will be likely to benefit from immunotherapy.
This study is being undertaken in an effort to evaluate breathprint analysis as a potential predicting factor for benefit from immunotherapy, so that treatment selection can further be improved.
This study is designed to help us identify the role of breathprint analysis to better select patients for immunotherapy.
Read the detailed description
Immune checkpoint blockade with anti-PD-1 and anti-PD-L1 antibodies has become a new standard of care in several cancer types as NSCLC and melanoma. However, in biomarker-unselected patient populations, overall response rate (ORR) depending on type of cancer and whether single or combination treatment is chosen remains still only 20%-60%. Though overall well tolerated approximately 5-10% of patients treated with PD1/PD-L1 targeting agents will experience grade 3 or 4 toxicities, including potentially life-threatening auto-immune toxicities such as colitis, hepatitis, and pneumonitis. Therefore, due to high costs of treatment and its possible complications, improved selection of patients is a crucial goal and an easily available non-invasive, point-of-care test for better patient selection is very much needed.
A promising approach in this regard is the analysis of volatile organic compounds (VOCs) in breath. Breath analysis for the detection of VOCs is increasingly investigated for its utility in diagnosis and management of cancer. Electronic noses (eNoses) are promising as cheap and clinically-practical devices that are designed to detect patterns of VOCs. Recently published prospective observational data showed very promising discriminant function for breathprint analysis for non-response to immunotherapy in NSCLC patients.
The principle goal of this study is to validate a prior study that found that breathomics-based classifiers predicted 12-week early progression vs non-progression in advanced NSCLC patients treated with nivolumab or pembrolizumab. Secondarily, we will expand assessment of breathomic-based classifiers to include other cohorts of advanced tumors treated with ICI, and also consider using response instead of non-progression as an endpoint. Exploratory goals include refinement of the breathomics classifier using alternative machine-learning techniques, and correlate with other biomarkers of immunotherapy outcomes.
- Conditions
- NSCLC, Melanoma, Kidney Cancer, Urothelial Carcinoma, Head and Neck Cancer
- Being tested
- Breathprint analysis and patient-reported outcomes
- Keywords
- breathprint analysis, immunotherapy, predictive biomarker
- Medical subject headings
- Melanoma, Kidney Neoplasms, Carcinoma, Transitional Cell, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Breathprint analysis and patient-reported outcomesOther
Breathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment.
Questionnaires will be completed at the same timepoints.
| Study group | Role | What they receive |
|---|---|---|
| Validation cohort: NSCLC | Patients with advanced/metastatic NSCLC planned for IO-treatment in one of the following categories
* Pembrolizumab monotherapy first-line
* Pembrolizumab or nivolumab monotherapy in second or later line Receives: Other: Breathprint analysis and patient-reported outcomes | |
| Cohort 1: NSCLC | Patients with advanced/metastatic NSCLC planned for Pembrolizumab-chemotherapy combination therapy first-line Receives: Other: Breathprint analysis and patient-reported outcomes | |
| Cohort 2: Melanoma | Patients with advanced/metastatic melanoma planned for IO-treatment in one of the following categories
* Nivolumab/ipilimumab combination treatment 1L
* Pembrolizumab or nivolumab monotherapy treatment 1L
* Ipilimumab monotherapy 2L Receives: Other: Breathprint analysis and patient-reported outcomes | |
| Cohort 3: Mixed solid tumor cohort | Patients with advanced/metastatic solid tumors such as Head\&Neck tumors, kidney cancer and urothelial cancer planned for IO-treatment Receives: Other: Breathprint analysis and patient-reported outcomes | |
| Cohort 4: NSCLC | Patients with advanced/metastatic NSCLC planned for treatment with Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy) Receives: Other: Breathprint analysis and patient-reported outcomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
12 week Progression Rate in validation cohort
Measured: 12 weeks
Secondary outcomes (2)
Overall Survival (OS) in validation cohort
Measured: 5 years
Overall Response Rate (ORR) in validation cohort
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2019
- Study start24 Feb 2020
- Primary completion9 Feb 2026
- Study completion9 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- University of Amsterdam
- Responsible party
- Sponsor
- Investigators
- Geoffrey Liu, MD MSc, Principal investigator, UHN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04146064
- Sponsor's protocol ID
- IO-Breathomics
- Other IDs
- 19-5936
- Status last verified
- May 2026
- First submitted
- 29 Oct 2019
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Breathomics as a Non-invasive, Inexpensive, Point-of-care Predictive Test for Immune Checkpoint Inhibitor Efficacy
- ClinicalTrials.gov ID
- NCT04146064
- Acronym / sponsor ID
- IO-Breathomics
- Conditions
- NSCLC, Melanoma, Kidney Cancer, Urothelial Carcinoma, Head and Neck Cancer
- Keywords
- breathprint analysis, immunotherapy, predictive biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 190 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- University of Amsterdam
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 9 Feb 2026 (actual)
- Study completion
- 9 Feb 2026 (actual)
- First posted
- 31 Oct 2019 (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.
Immunotherapy with agents stimulating the immune system to act against cancer are now a new standard of care in various cancers as lung cancer and melanoma, but also bladder cancer, kidney cancer and head \& neck cancer. However, even though a subset of patients derives long-term benefit from these agents, depending of cancer type still at least half of patients do not respond to these new drugs. Our understanding of possible factors predicting whether a patient might actually benefit from immunotherapy is poor. Volatile organic compounds (VOCs) are gases exhaled with a person's breath, which are released into the lung from blood and bacteria and therefore can give information about infections as well as inflammation and possibly cancer cells in a person's body. Breath analysis of these VOCs with special devices called electronic noses (eNose) generate a specific electric signals patterns called breathprints. There is early evidence that specific breathprints can actually help to select patients who will be likely to benefit from immunotherapy.
This study is being undertaken in an effort to evaluate breathprint analysis as a potential predicting factor for benefit from immunotherapy, so that treatment selection can further be improved.
This study is designed to help us identify the role of breathprint analysis to better select patients for immunotherapy.
Detailed description
Immune checkpoint blockade with anti-PD-1 and anti-PD-L1 antibodies has become a new standard of care in several cancer types as NSCLC and melanoma. However, in biomarker-unselected patient populations, overall response rate (ORR) depending on type of cancer and whether single or combination treatment is chosen remains still only 20%-60%. Though overall well tolerated approximately 5-10% of patients treated with PD1/PD-L1 targeting agents will experience grade 3 or 4 toxicities, including potentially life-threatening auto-immune toxicities such as colitis, hepatitis, and pneumonitis. Therefore, due to high costs of treatment and its possible complications, improved selection of patients is a crucial goal and an easily available non-invasive, point-of-care test for better patient selection is very much needed.
A promising approach in this regard is the analysis of volatile organic compounds (VOCs) in breath. Breath analysis for the detection of VOCs is increasingly investigated for its utility in diagnosis and management of cancer. Electronic noses (eNoses) are promising as cheap and clinically-practical devices that are designed to detect patterns of VOCs. Recently published prospective observational data showed very promising discriminant function for breathprint analysis for non-response to immunotherapy in NSCLC patients.
The principle goal of this study is to validate a prior study that found that breathomics-based classifiers predicted 12-week early progression vs non-progression in advanced NSCLC patients treated with nivolumab or pembrolizumab. Secondarily, we will expand assessment of breathomic-based classifiers to include other cohorts of advanced tumors treated with ICI, and also consider using response instead of non-progression as an endpoint. Exploratory goals include refinement of the breathomics classifier using alternative machine-learning techniques, and correlate with other biomarkers of immunotherapy outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Validation cohort: NSCLC | – | Other: Breathprint analysis and patient-reported outcomesPatients with advanced/metastatic NSCLC planned for IO-treatment in one of the following categories * Pembrolizumab monotherapy first-line * Pembrolizumab or nivolumab monotherapy in second or later line |
| Cohort 1: NSCLC | – | Other: Breathprint analysis and patient-reported outcomesPatients with advanced/metastatic NSCLC planned for Pembrolizumab-chemotherapy combination therapy first-line |
| Cohort 2: Melanoma | – | Other: Breathprint analysis and patient-reported outcomesPatients with advanced/metastatic melanoma planned for IO-treatment in one of the following categories * Nivolumab/ipilimumab combination treatment 1L * Pembrolizumab or nivolumab monotherapy treatment 1L * Ipilimumab monotherapy 2L |
| Cohort 3: Mixed solid tumor cohort | – | Other: Breathprint analysis and patient-reported outcomesPatients with advanced/metastatic solid tumors such as Head\&Neck tumors, kidney cancer and urothelial cancer planned for IO-treatment |
| Cohort 4: NSCLC | – | Other: Breathprint analysis and patient-reported outcomesPatients with advanced/metastatic NSCLC planned for treatment with Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects included in this study are patients over the age of 18 years with a histologically-confirmed diagnosis of non-small cell lung cancer, melanoma or other solid tumor for which ICI-treatment is a standard of care. Patients must have advanced/metastatic disease and planning to receive ICI treatment (categories defined above) or chemotherapy treatment (cohort 4) at the Princess Margaret Cancer Centre/University Health Network. Study subjects will be consented specifically for that study.
Key inclusion criteria (9 listed)
- Patients 18 years of age or older
- Histologically confirmed advanced/metastatic non-small cell lung cancer, melanoma or solid tumor such as urothelial, kidney or head and neck cancer and planned treatment with
- At least one measurable lesion as defined by RECIST 1.1. A lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation.
- Able to provide informed consent.
Key exclusion criteria (3 listed)
- Patients who are unable to perform the breathing manoeuvres needed for eNose-analysis of exhaled air.
- Patients who are unable to independently consent to participation in the trial.
- Patients with severe, acute, or chronic medical conditions (including uncontrolled diabetes mellitus) or psychiatric conditions or laboratory abnormalities that in the opinion of the Investigator or their physician may cause undue harm or inconvenience to the patient, or that may interfere with the interpretation of study results.
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 |
|---|---|---|
| Breathprint analysis and patient-reported outcomesBreathprint analysis: Patients will be providing breathprint samples into the eNose device at baseline and every 12 weeks thereafter as long as on immunotherapy treatment. Questionnaires will be completed at the same timepoints. | Other | Cohort 1: NSCLC, Cohort 2: Melanoma, Cohort 3: Mixed solid tumor cohort, Cohort 4: NSCLC, Validation cohort: NSCLC |
Primary outcome
12 week Progression Rate in validation cohort
Time frame: 12 weeks
2 secondary outcomes
Overall Survival (OS) in validation cohort
Time frame: 5 years
Overall Response Rate (ORR) in validation cohort
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: Undecided
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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.
Geoffrey Liu, MD MSc principal investigator
UHN
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 NSCLC and Melanoma, run by University Health Network, Toronto at 1 site in Canada.
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 9 inclusion and 3 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 8 May 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
12 week Progression Rate in validation cohort (time frame: 12 weeks). 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 8 May 2026.