Open-label, Uncontrolled, Non-Interventional, Retrospective Study to Evaluate Molecular Determinants of Outcome to the Immune Checkpoint Inhibitors (Anti-PD-1/Anti-PD-L1 Monoclonal Antibodies) Treatment for Solid Tumors

The recent approval of ICB treatments targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1/PD-L1) by the US Food and Drug Administration has offered an improved treatment chance for a variety of malignant tumors, including those with a particularly poor prognosis. However, a growing number of studies and case reports show that immunotherapy may accelerate tumor progression in a significant subset of patients ranging from 9% to 27% across multiple histologies and lead to so-called hyperprogressive disease (HPD) that leads to a rapid patient death.

During this NIS study, Asylia Diagnostics aims to fill in the first layer of knowledge leading to the identification of predictive biomarkers and biological mechanisms that could be used for the prediction, diagnosis, and treatment of melanoma and NSCLC HPD patients.

The study is a retrospective clinical study. During this study basic historical medical information and scrolls from FFPE-preserved biopsies taken prior to immunotherapy treatment will be collected. The nature of the study is not invasive and non interruptive to the standard of care.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Lung Cancer
• Intervention / Treatment: Drug: Pembrolizumab

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Andrey Khmelevskiy, MSc; Phone Number: +32 492 40 40 24; Email: andrey.khmelevskiy@asyliadx.com

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • Universitair Ziekenhuis Antwerpen
    • Contact: Vasiliki Siozopoulou, Dr.; Phone Number: +32 3 821 37 53; Email: Vasiliki.Siozopoulou@uza.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects treated by immune checkpoint inhibitors

Description

Inclusion Criteria:

• Females and males 18-95 y.o.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >/=70%)
• Histologically or cytologically confirmed melanoma or lung cancer, the grade of the tumor, diagnosed before enrolment into the study.
• Treatment with anti-PD1/anti-PD-L1 drugs and anti-PD1/anti-PD-L1 drugs in combinations with other therapies
• Subjects may have received any number of prior lines of chemotherapy or targeted therapies
• Availability of FFPE tissue samples received prior to any type of antitumor treatment start
• Complete medical records (stage, receptors status, demographic data)

Exclusion Criteria:

• Has had chemotherapy, targeted small molecule therapy, or radiation therapy >30 Gray within 14 days prior to the baseline biopsy or persistent adverse events (AE) related to prior therapy, which have not recovered (i.e., AEs should be ≤Grade 1 or ≤the value collected at baseline) from AEs due to a previously administered intervention
• Any evidence of uncontrolled system pathology, active infections, active bleeding diathesis, renal graft, hepatitis B, C or HIV.
• Autoimmune diseases such as Addison's disease, thyroiditis, lupus (SLE), Sjogren's syndrome, scleroderma, myasthenia gravis, Grave's disease, and Goodpasture's syndrome, requiring active therapy with corticosteroids. If a patient has been taking steroids, at least 2 weeks must have passed since the last dose. Patients with a history of endocrinopathies (e.g. hypothyroidism, adrenal insufficiency, hypopituitarism) are eligible if they are stable on hormone replacement therapy.
• Patients with prior splenectomy, ocular melanoma
• Recent (within 1 year) history of another cancer with the exceptions of non-melanoma skin cancer, superficial bladder cancer, or localized cervical cancer
• Pregnant patients

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RECIST	Response Evaluation Criteria in Solid Tumours	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression free survival	24 weeks

Collaborators and Investigators

• Sponsor: Asylia Diagnostics BV

Publications and helpful links

General Publications

• Borcoman E, Kanjanapan Y, Champiat S, Kato S, Servois V, Kurzrock R, Goel S, Bedard P, Le Tourneau C. Novel patterns of response under immunotherapy. Ann Oncol. 2019 Mar 1;30(3):385-396. doi: 10.1093/annonc/mdz003.
• Champiat S, Besse B, Marabelle A. Hyperprogression during immunotherapy: do we really want to know? Ann Oncol. 2019 Jul 1;30(7):1028-1031. doi: 10.1093/annonc/mdz184. No abstract available.
• Champiat S, Ferrara R, Massard C, Besse B, Marabelle A, Soria JC, Ferte C. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat Rev Clin Oncol. 2018 Dec;15(12):748-762. doi: 10.1038/s41571-018-0111-2.
• Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review. JAMA Oncol. 2016 Oct 1;2(10):1346-1353. doi: 10.1001/jamaoncol.2016.1051.
• Fuentes-Antras J, Provencio M, Diaz-Rubio E. Hyperprogression as a distinct outcome after immunotherapy. Cancer Treat Rev. 2018 Nov;70:16-21. doi: 10.1016/j.ctrv.2018.07.006. Epub 2018 Jul 18.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2020
• Primary Completion (ANTICIPATED): June 6, 2022
• Study Completion (ANTICIPATED): June 6, 2023

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (ACTUAL): April 26, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pembrolizumab; Ipilimumab
• Other Study ID Numbers: BR00012020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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