POINTING: Clinical Cohort Study of Patients With Melanoma and NSCLC Receiving Checkpoint Inhibitors

Study Overview
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Brief Summary
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This is a two-center, prospective continuously accruing longitudinal cohort study in patients with non-small cell lung carcinoma (NSCLC) or metastatic melanoma eligible for standard anti-PD-1 antibody treatment. The data from this prospective longitudinal cohort will be used in the POINTING (towards patient -tailored cancer immunotherapy supported by a multifaceted predictive signature composed of integrative omics and molecular imaging) KWF Kankerbestrijding project (WP4). The goal of this project is to develop a multifaceted predictive signature, by using new techniques on tumor characteristics before and during treatment with immune therapy. To do so, researchers will use the 'omics' approach. By combining molecular omics comprising genomics, transcriptomics, proteomics with radiomics and molecular imaging a set of factors will arise which can accurately predict the outcome of the treatment. Participants in this cohort will undergo tumor biopsies, venous blood sampling and feces sampling before, during and at the end of standard anti-PD-1 antibody treatment. Also, data derived form routine procedures performed for standard-of-care anti-PD-1 treatment (ao laboratory assessments, CT and FDG-PET) will be collected.

Official Title
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Towards Patient-tailored Cancer Immunotherapy Supported by a Multifaceted Predictive Signature Composed of Integrative Omics and Molecular Imaging

Conditions
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Melanoma, Non-Small Cell Lung Cancer

Intervention / Treatment
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* Other: Standard-of-care procedures
* Other: Study procedures


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytological documented locally advanced or metastatic melanoma or NSCLC. Patients must be eligible for standard treatment with anti-PD-1 antibody treatment (monotherapy or in combination with other checkpoint inhibitors). Age ≥18 years. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions. Metastatic or locally advanced lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures. Ability to comply with protocol. Signed Informed Consent form. Exclusion Criteria: Malignancies other than melanoma or NSCLC within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent or ductal carcinoma in situ treated surgically with curative intent). Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to study inclusion. Patients who have received acute, low-dose, systemic immunosuppressant medications may be enrolled. The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| POINTING<br> | Other: Standard-of-care procedures<br>* Patients receive standard of care anti-PD-1 treatment as monotherapy or in combination with other checkpoint inhibitors. Related assessments, as laboratory assessments, CT-thorax-abdomen and FDG-PET will be performed according to clinical routine procedures.<br>Other: Study procedures<br>* Patients will undergo tumor biopsies, venous blood sampling and feces sampling in combination with a food questionnaire before, during and at the end of standard of care anti-PD-1 treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive signatures based on multi-omics for PD-1 antibody treatment response as assessed by RECIST1.1 | The aim of this clinical cohort is to develop and validate multifaceted predictive signatures for PD-1 antibody effects with relevant components of integrative omics (histology, immunohistochemistry, genomics, transcriptomics, proteomics, radiomics and/or molecular imaging), which predict, which patients have a ≤ 5% chance of responding to anti-PD-1 antibody treatment. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2. Predictive signatures based on multi-omics for PD-1 antibody treatment toxicity as assessed by CTCAE 4.03. | As secondary aim, the relation between multifaceted signatures composed by relevant components of integrative omics (histology, immunohistochemistry, genomics, transcriptomics, proteomics, radiomics and/or molecular imaging) and toxicity of PD-1 antibody treatment will be assessed. Toxicity will be scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Anti-PD1 checkpoint inhibitor