Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments, Using Multiomics

Study Overview
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Brief Summary
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The goal of this exploratory study is understand the mechanisms of response to immunotherapy in Non-Small Cell Lung Cancer patients. The investigators are going to search for correlation between specific biological features and response to immunotherapy, and to use those associations for developing an algorithm enabling to identify patients that could benefit from the immune check inhibitor based anti cancer treatment. Patients will provide biological samples before and during their treatment, and clinical data will be collected.

Detailed Description
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The goal of the study is to develop an algorithm that associates between biomarkers detected in biospecimen of NSCLC patients, and their: Response to treatment Clinical benefit parameters such as PFS and OS. Adverse events to immune check inhibitor therapy Biological mechanisms involved in response or resistance to immune check inhibitor therapy. Patients will provide plasma, PBMCs, stool and tissue samples (where applicable) before and during treatment. Clinical data, including disease history, given treatment, response evaluation and adverse events to the treatment will be recorded. Samples will be analysed as follows - Proteomic features (Plasma proteomics) Epigenetic patterns (cell free DNA) ctDNA mutation analysis PBMC subpopulations Microbiome profiling (Stool)

Official Title
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PROPHETIC Extended - Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments, Extended Study.

Conditions
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Non Small Cell Lung Cancer, Healthy

Intervention / Treatment
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* Other: blood, stool and tissue samples collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study-specific procedures. Male or female aged at least 18 years. ECOG PS - 0/1-2. Exclusion Criteria: Any concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of treatment. Generalized impairment or mental incompetence that would render the patient unable to understand his/her participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-operable NSCLC patients receiving ICI therapy<br>Patients with non-operable stage IIIB-IV NSCLC treated with immune check inhibitor anti cancer treatment as a standard of care | Other: blood, stool and tissue samples collection<br>* blood, stool and tissue samples collection before and during the treatment, as applicable<br>|
| Operable NSCLC Patients Receiving ICI as Neoadjuvant or Adjuvant Therapy<br>Patients with operable stage II-IIIA NSCLC, treated with immune check inhibitor in the neoadjuvant or adjuvant setting | Other: blood, stool and tissue samples collection<br>* blood, stool and tissue samples collection before and during the treatment, as applicable<br>|
| Healthy volunteers<br>Sex and aged matched non-diseased volunteers | Other: blood, stool and tissue samples collection<br>* blood, stool and tissue samples collection before and during the treatment, as applicable<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 3 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 6 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 9 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 12 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 15 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 18 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 21 | 
| Overall response (OR) | OR as defined by RECIST 1.1 or any other validated clinical scale for response | month 24 | 
| Plasma proteomic profile | Plasma proteins measurments | Baseline, pre treatment | 
| Plasma proteomic profile | Plasma proteins measurments | 2(+/-1) weeks from first treatment | 
| Plasma proteomic profile | Plasma proteins measurments | 3 months | 
| Plasma proteomic profile | Plasma proteins measurments | 6 months | 
| Plasma proteomic profile | Plasma proteins measurments | 9 months | 
| Plasma proteomic profile | Plasma proteins measurments | 12 months | 
| Plasma proteomic profile | Plasma proteins measurments | 15 months | 
| Plasma proteomic profile | Plasma proteins measurments | 18 months | 
| Plasma proteomic profile | Plasma proteins measurments | 21 months | 
| Plasma proteomic profile | Plasma proteins measurments | 24 months | 
| Epigenetic patterns | Characterization of Cell free DNA | Baseline, pre treatment | 
| Epigenetic patterns | Characterization of Cell free DNA | 2(+/-1) weeks from first treatment | 
| Epigenetic patterns | Characterization of Cell free DNA | 12 months | 
| Epigenetic patterns | Characterization of Cell free DNA | 24 months | 
| ctDNA mutation analysis | ctDNA mutation analysis | immediately after surgery | 
| Microbiome profiling | PBMC subpopulations exploration | Baseline, pre treatment | 
| Microbiome profiling | PBMC subpopulations exploration | 2(+/-1) weeks from first treatment | 
| Microbiome profiling | PBMC subpopulations exploration | 12 months | 
| Microbiome profiling | PBMC subpopulations exploration | 24 months |