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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Non-Small Cell Lung Cancer
• Intervention / Treatment: Other: Standard-of-care procedures; Other: Study procedures

• Study Type: Observational
• Enrollment (Estimated): 3500

Contacts and Locations

• Study Contact: Name: R. S.N. Fehrmann, MD, PhD; Phone Number: +31 50 361 2821; Email: r.s.n.fehrmann@umcg.nl
• Study Contact Backup: Name: E. G.E. de Vries, MD, PhD; Phone Number: +31 50 361 2821; Email: e.g.e.de.vries@umcg.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • NKI-AvL
    • Contact: J. B.A.G. Haanen, MD, PhD; Phone Number: +31 20 512 9111; Email: j.haanen@nki.nl
    • Principal Investigator: J. B.A.G. Haanen, MD, PhD
  • Groningen, Netherlands
    • Recruiting
    • University Medical Center Groningen
    • Contact: R. S.N. Fehrmann, MD, PhD; Phone Number: +31 50 361 2821; Email: r.s.n.fehrmann@umcg.nl
    • Contact: E. G.E. de Vries, MD, PhD; Phone Number: +31 50 361 2821; Email: e.g.e.de.vries@umcg.nl
    • Principal Investigator: E. G.E. de Vries, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with locally advanced or metastatic melanoma or metastatic NSCLC, who are eligible to receive anti-PD-1 antibody treatment as monotherapy or in combination with other checkpoint inhibitors.

Description

Inclusion criteria:

1. Histologically or cytological documented locally advanced or metastatic melanoma or NSCLC.
2. Patients must be eligible for standard treatment with anti-PD-1 antibody treatment (monotherapy or in combination with other checkpoint inhibitors).
3. Age ≥18 years.
4. Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
5. Metastatic or locally advanced lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
6. Ability to comply with protocol.
7. Signed Informed Consent form.

Exclusion Criteria:

1. 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).

2. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

POINTING

Other: Standard-of-care procedures; 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.; Other: Study procedures; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Study Chair: E. G.E. de Vries, MD, PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: September 24, 2018
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Anti-PD1 checkpoint inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: POINTING

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No