Genetic Predictors of Efficiency and Safety of ICIs in Patients With Different Malignancies (ICIPRESIST-0519)

• Conditions: Melanoma; Hodgkin Lymphoma; Squamous Cell Lung Cancer; Uveal Melanoma
• Interventions: Genetic: Genetic tests of the available tumor and plasma samples

• Registration Number: NCT04025424
• Lead Sponsor: Russian Academy of Medical Sciences

Brief Summary

This is a multicenter, non-interventional, retrospective study (with two prospective cohorts), including previously treated patients with melanoma, squamous cell lung cancer in the late stages (inoperable or metastatic) and Hodgkin disease at any stages.

The duration of the follow-up will be 12-60 months. Data from medical records will be retrospectively collected at different points in time. The first data extraction will consist of collecting data from the initial level (before treatment with immune checkpoints inhibitors (anti-PD1 / PDl1) before the end of the recruitment period for this study (up to 3 years of follow-up). Two additional annual data collections are planned for display additional follow-up and data for patients who will survive.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-15
• Study First Submitted: 2019-07-17
• Study First Submitted QC: 2019-07-17
• Study First Posted: 2019-07-18
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-26
• Last Update Posted: 2021-12-28
• Primary Completion: 2022-06-30
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

To participate in this study, the patient must meet the following criteria:

• At least 2 injections (or 10 weeks) of ICI (PD1, PDl1 blockers, including but not limited to such drugs as nivolumab, pembrolizumab, prolglimab, atezolizumab, avelumab, durvalumab, spratalizumab)
• Deceased patients meet the criteria; signing the informed consent of the legal representative of the deceased patient is not required

Specific inclusion criteria for individual cohorts:

• Cohort 1 (retrospective cohort of skin melanoma patients)

  • 1. Clinically and morphologically verified diagnosis of skin melanoma or melanoma metastases without an identified primary focus;
  • 2. The availability of basic clinical information about the patient and the course of his illness;
  • 3. Therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy (at least 2 injections);
  • 4. Evaluation of the effect of immunotherapy
  • 5. Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies, obtained no earlier than 24 months. before initiating therapy with a PD-1 or PD-L1 inhibitor;
  • 8. Patient-signed informed consent in case the patient is alive

• Cohort 2 (Hodjkin disease - retrospective)

  • 1. Clinically and morphologically verified diagnosis of Hodgkin disease (any histological variant);
  • 2. The availability of basic clinical information about the patient and the course of his illness;
  • 3. Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies;
  • 4. Patient signed informed consent.

• Cohort 3 (Uveal melanoma - retro)

  • 1. Clinically and morphologically verified diagnosis of uveal melanoma (any histological variant);
  • 2. The availability of basic clinical information about the patient and the course of his illness;
  • 3. Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic studies;
  • 4. Patient signed informed consent.

• Cohort 4 (melanoma of the skin - prospective)

  • 1. Clinically and morphologically verified diagnosis of metastatic melanoma;
  • 2. The availability of basic clinical information about the patient and the course of his illness;
  • 3. Indications for therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy;
  • 4. The possibility of including the patient in the present study before the first course of immunotherapy;
  • 5. Availability of tumor material (paraffin blocks and histological glass preparations) for morphological, immunohistochemical and molecular genetic studies obtained no earlier than 2 years before the planned start of immunotherapy with a standard PD-1 inhibitor;
  • 6. Separate patient consent to a repeated biopsy of the tumor focus before the planned start of immunotherapy with a PD-1 or PD-L1 inhibitor, if the existing tumor material was obtained earlier than 2 years before the planned start of immunotherapy
  • 7. Availability of samples of biological fluids collected before the start of immunotherapy and after the first course of immunotherapy for molecular genetic studies of circulating tumor DNA;
  • 8. Evaluation of the effect of therapy in the framework of local practice in accordance with the criteria of RECIST 1.1
  • 9. Signed by the patient informed consent to participate in the study.

• Cohort 5 (squamous cell lung cancer - prospective)

  • 1. Clinically and morphologically verified diagnosis of metastatic or inoperable squamous cell lung cancer;
  • 2. The availability of basic clinical information about the patient and the course of his illness;
  • 3. The presence of indications for therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy;
  • 4. The possibility of including the patient in the present study before the first course of immunotherapy;
  • 5. Availability of tumor material (paraffin blocks) for morphological, immunohistochemical and molecular genetic research, obtained no earlier than 2 years before the planned start of immunotherapy with a standard PD-1 inhibitor;
  • 6. Separate patient consent to a repeated biopsy of the tumor focus before the planned start of immunotherapy with a PD-1 or PD-L1 inhibitor, if the existing tumor material was obtained earlier than 2 years before the planned start of immunotherapy
  • 7. Availability of samples of biological fluids collected before the start of immunotherapy and after the first course of immunotherapy for molecular genetic studies of circulating tumor DNA;
  • 8. Evaluation of the effect of therapy in the framework of local practice in accordance with the criteria of RECIST 1.1
  • 9. Signed by the patient informed consent to participate in the study.

Exclusion Criteria

• Cohort 1 (retrospective cohort of skin melanoma patients)

  • 1. It is not allowed to conduct other immunotherapy (anti-CTLA4, vaccines, etc.) to patients before the course of therapy with a PD-1 or PD-L1 inhibitor in a standard dosage in monotherapy

• Cohort 2 (Hodgkin disease - retrospective)

• no special exclusion criteria

• Cohort 3 (Uveal melanoma - retro)

  • No special exclusion criteria.

• Cohort 4 (melanoma of the skin - prospective)

  • 1. It is not allowed to include patients who have previously undergone other immunotherapy (anti-CTLA4, vaccines, etc.) before the course of therapy with the PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy
  • 2. It is not allowed to include patients who are scheduled for combination immunotherapy (anti-PD1 + anti-CTLA4, vaccines, etc.) after inclusion in this study

• Cohort 5 (squamous cell lung cancer - prospective)

  • 1. It is not allowed to include patients who have previously undergone other immunotherapy (anti-CTLA4, vaccines, etc.) before the course of therapy with the PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy
  • 2. It is not allowed to include patients who are scheduled for combination immunotherapy (anti-PD1 + anti-CTLA4, vaccines, etc.) after inclusion in this study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hodgkin disease, retrospective	Genetic tests of the available tumor and plasma samples	* 1) Clinically and morphologically verified diagnosis of Hodgkin disease (any histological variant); * 2) The availability of basic clinical information about the patient and the course of his illness;
Skin melanoma, retrospective	Genetic tests of the available tumor and plasma samples	* 1) Clinically and morphologically verified diagnosis of skin melanoma or melanoma metastases without an identified primary lesion; * 2) The availability of basic clinical information about the patient and the course of his illness;
Skin melanoma, proscpective	Genetic tests of the available tumor and plasma samples	* 1) Clinically and morphologically verified diagnosis of metastatic melanoma; * 2) The availability of basic clinical information about the patient and the course of his illness;
Lung cancer, procpective	Genetic tests of the available tumor and plasma samples	* 1) Clinically and morphologically verified diagnosis of metastatic or inoperable squamous cell lung cancer; * 2) The availability of basic clinical information about the patient and the course of his illness; * 3) The presence of indications for therapy with a PD-1 or PD-L1 inhibitor in the standard dosage in monotherapy;
Uveal melanoma, retrospective	Genetic tests of the available tumor and plasma samples	* 1) Clinically and morphologically verified diagnosis of uveal melanoma (any histological variant); * 2) The availability of basic clinical information about the patient and the course of his il

Primary Outcome Measures

Name	Time	Method
overall survival (OS) of patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and lymphoma granulomatosis	dec 2021	Overall survival (OS) will be calculated and presented in graphical form using the method of the product of Kaplan-Meier limits. The report will include a median of C with corresponding bilateral values of 95% CI. The proportion of patients who survive at certain points in time (1, 2, and 3 years), as well as the corresponding bilateral values of 95% CI, will be evaluated and reported.
incidence and severity of all adverse events (AEs) in patients receiving immune checkpoint blockers (PD1 / PDl1 blockers) in the first and subsequent treatment lines in patients with metastatic or unresectable melanoma, lung cancer and lymphoma.	dec 2021

Trial Locations

Locations (1)

N.N. Blokhin Russian Cancer Research Center; 🇷🇺 Moscow', Москва, Russian Federation