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

• ClinicalTrials.gov Identifier: NCT04860076
• Recruitment Status: Recruiting
• First Posted: April 26, 2021
• Last Update Posted: April 26, 2021
• Sponsor: Asylia Diagnostics BV
• Information provided by (Responsible Party): Asylia Diagnostics BV

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Melanoma; Lung Cancer	Drug: Pembrolizumab

Study Design

• Study Type: Observational
• Estimated Enrollment: 400 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: 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
• Actual Study Start Date: June 6, 2020
• Estimated Primary Completion Date: June 6, 2022
• Estimated Study Completion Date: June 6, 2023

Groups and Cohorts

Intervention Details:

• Drug: Pembrolizumab
  Standard of care
  Other Names:

  • Ipilimumab
  • Nivolumab

Outcome Measures

Primary Outcome Measures :

1. RECIST [ Time Frame: 24 weeks ]
   Response Evaluation Criteria in Solid Tumours

Secondary Outcome Measures :

1. PFS [ Time Frame: 24 weeks ]
   Progression free survival

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Subjects treated by immune checkpoint inhibitors

Criteria

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

Contacts and Locations

Contacts

Contact: Andrey Khmelevskiy, MSc; +32 492 40 40 24; andrey.khmelevskiy@asyliadx.com

Locations

Belgium

Universitair Ziekenhuis Antwerpen; Recruiting

Edegem, Belgium, 2650

Contact: Vasiliki Siozopoulou, Dr. +32 3 821 37 53 Vasiliki.Siozopoulou@uza.be

Sponsors and Collaborators

Asylia Diagnostics BV

More Information

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.

Champiat S, Ferrara R, Massard C, Besse B, Marabelle A, Soria JC, Ferté 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. Review.

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. Review.

Fuentes-Antrás J, Provencio M, Díaz-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. Review.

• Responsible Party: Asylia Diagnostics BV
• ClinicalTrials.gov Identifier: NCT04860076
• Other Study ID Numbers: BR00012020
• First Posted: April 26, 2021
• Last Update Posted: April 26, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Pembrolizumab; Nivolumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action