Biomarkers for the Activity of Immune Checkpoint Inhibitor Therapy in Patients With Advanced Melanoma (ICIT)

1. Screen and recruitment: patients will be screened based on their prior history and intention to initiate treatment with an immune checkpoint inhibitor.

2. Study phase:

   • Collection of baseline demographic data, prior disease history, nature of ICI therapy, outcome data of ICI therapy (treatment disposition, toxicity, tumor response and survival).
   • Collection of blood samples will be performed every 3 to 4 weeks for the first year on ICI therapy and every 6 to 12 weeks thereafter until the end of ICI therapy, disease progression, death or loss to follow-up. Collection of blood samples will be aligned with the visits necessary for the administration of the ICI therapy.
   • Collection of archival melanoma metastasis tissues will be performed on a continuous basis and be triggered by availability of such tissue following therapeutic resections of melanoma metastases.
3. Follow-up phase

Study Overview

• Status: Recruiting
• Conditions: Malignant Melanoma

Detailed Description

1. Screen and recruitment: patients will be screened based on their prior history and intention to initiate treatment with an immune checkpoint inhibitor. This screening of candidate patients by the investigators will be non-interventional. Patients that are considered eligible candidates will be invited to participate in this study and to Page 3/18 provide written informed consent.

2. Study phase:

   • Collection of baseline demographic data, prior disease history, nature of ICI therapy, outcome data of ICI therapy (treatment disposition, toxicity, tumor response and survival).
   • Collection of blood samples will be performed every 3 to 4 weeks for the first year on ICI therapy and every 6 to 12 weeks thereafter until the end of ICI therapy, disease progression, death or loss to follow-up. Collection of blood samples will be aligned with the visits necessary for the administration of the ICI therapy.
   • Collection of archival melanoma metastasis tissues will be performed on a continuous basis and be triggered by availability of such tissue following therapeutic resections of melanoma metastases.
3. Follow-up phase: patients who stop treatment with the immune checkpoint inhibitor will be followed-up for

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Bart Neyns, MD; PhD; Phone Number: 024746040; Email: bart.neyns@uzbrussel.be
• Study Contact Backup: Name: Yanina Jansen, MD; Phone Number: 024746040; Email: yanina.jansen@uzbrussel.be

Study Locations

• Belgium
  • Brabant
    • Jette, Brabant, Belgium, 1090
      • Recruiting
      • UZ Brussel
  • Brussels
    • Jette, Brussels, Belgium, 1090
      • Recruiting
      • UZ Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patient with an unresectable stage III or stage IV melanoma treated with pembrolizumab

Description

Inclusion Criteria:

1. Histologically confirmed malignant melanoma;
2. AJCC Stage IIIC or IV melanoma with evaluable disease;
3. Treatment with an immune checkpoint inhibitor;
4. Willing and able to give written informed consent;
5. Accessible for treatment and follow-up;

Exclusion Criteria:

• non

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
observational arm; From start treatment till date of death or date of cure, the patient will be followed for survival and adverse events on pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
explore the value of biomarkers present in blood, and tumor tissue for the purpose of predicting the efficacy of ICI therapy or for the purpose of monitoring the therapeutic effect of ICI therapy	explore the value of biomarkers present in blood, and tumor tissue for the purpose of predicting the efficacy of ICI therapy or for the purpose of monitoring the therapeutic effect of ICI therapy	1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline demographic data, prior disease history, nature of ICI therapy, treatment disposition, adverse events	Baseline demographic data, prior disease history, nature of ICI therapy, treatment disposition, adverse events	1year
Tumor response according to the RECISTv1.1 and irRC criteria	Tumor response according to the RECISTv1.1 and irRC criteria	1 year
Survival (PFS, and OS) by Kaplan-Meier estimates	Survival (PFS, and OS) by Kaplan-Meier estimates	1year
Data collection on the nature and disposition of ICI therapy as well as its efficacy and treatment related adverse events will be collected on a non-interventional basis	Data collection on the nature and disposition of ICI therapy as well as its efficacy and treatment related adverse events will be collected on a non-interventional basis	1 year

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Bart NEyns, MD; PhD, Universitair Ziekenhuis Brussel

Publications and helpful links

General Publications

• Wilgenhof S, Du Four S, Vandenbroucke F, Everaert H, Salmon I, Lienard D, Marmol VD, Neyns B. Single-center experience with ipilimumab in an expanded access program for patients with pretreated advanced melanoma. J Immunother. 2013 Apr;36(3):215-22. doi: 10.1097/CJI.0b013e31828eed39.
• Ribas A, Kefford R, Marshall MA, Punt CJ, Haanen JB, Marmol M, Garbe C, Gogas H, Schachter J, Linette G, Lorigan P, Kendra KL, Maio M, Trefzer U, Smylie M, McArthur GA, Dreno B, Nathan PD, Mackiewicz J, Kirkwood JM, Gomez-Navarro J, Huang B, Pavlov D, Hauschild A. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. J Clin Oncol. 2013 Feb 10;31(5):616-22. doi: 10.1200/JCO.2012.44.6112. Epub 2013 Jan 7.
• Weber JS, Kudchadkar RR, Yu B, Gallenstein D, Horak CE, Inzunza HD, Zhao X, Martinez AJ, Wang W, Gibney G, Kroeger J, Eysmans C, Sarnaik AA, Chen YA. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol. 2013 Dec 1;31(34):4311-8. doi: 10.1200/JCO.2013.51.4802. Epub 2013 Oct 21.
• Jansen YJL, Rozeman EA, Mason R, Goldinger SM, Geukes Foppen MH, Hoejberg L, Schmidt H, van Thienen JV, Haanen JBAG, Tiainen L, Svane IM, Makela S, Seremet T, Arance A, Dummer R, Bastholt L, Nyakas M, Straume O, Menzies AM, Long GV, Atkinson V, Blank CU, Neyns B. Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma. Ann Oncol. 2019 Jul 1;30(7):1154-1161. doi: 10.1093/annonc/mdz110.
• de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, Bravenboer B. Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab. J Clin Endocrinol Metab. 2016 Nov;101(11):4431-4439. doi: 10.1210/jc.2016-2300. Epub 2016 Aug 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ANTICIPATED): September 1, 2025
• Study Completion (ANTICIPATED): December 1, 2025

Study Registration Dates

• First Submitted: February 1, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (ESTIMATE): February 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2014-BN-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES