Breathomics as Predictive Biomarker for Checkpoint Inhibitor Response

Recruiting

• Conditions: Melanoma; Urothelial Carcinoma; Head and Neck Cancer; NSCLC; Kidney Cancer
• Interventions: Other: Breathprint analysis and patient-reported outcomes

• Registration Number: NCT04146064
• Lead Sponsor: University Health Network, Toronto

Brief 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. 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 Timeline

• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-10-29
• Study First Posted: 2019-10-31
• Study Start: 2020-02-24
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-02
• Last Update Posted: 2023-06-05
• Primary Completion: 2024-05
• Study Completion: 2024-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 425

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 3: Mixed solid tumor cohort	Breathprint analysis and patient-reported outcomes	Patients with advanced/metastatic solid tumors such as Head\&Neck tumors, kidney cancer and urothelial cancer planned for IO-treatment
Cohort 4: NSCLC	Breathprint analysis and patient-reported outcomes	Patients with advanced/metastatic NSCLC planned for treatment with Chemotherapy-only (either platinum-based combination treatment or docetaxel monotherapy)
Validation cohort: NSCLC	Breathprint analysis and patient-reported outcomes	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
Cohort 1: NSCLC	Breathprint analysis and patient-reported outcomes	Patients with advanced/metastatic NSCLC planned for Pembrolizumab-chemotherapy combination therapy first-line
Cohort 2: Melanoma	Breathprint analysis and patient-reported outcomes	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

Primary Outcome Measures

Name	Time	Method
12 week Progression Rate in validation cohort	12 weeks

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) in validation cohort	5 years
Overall Response Rate (ORR) in validation cohort	5 years

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada