A Prospective Study of the Relevance of the HLA-G Immune Checkpoint in Cancer Immunotherapy

Overview

Therapeutic targeting of immune checkpoints PD-1/PD-L1 and/or CTLA-4 is efficient in several solid cancer subtypes, however only some patients do experience clinical benefit from these treatments. One explanation could be that multiple redundant checkpoints are present within the tumor, simultaneously keeping in check the patient's immune response. The immune checkpoint HLA-G is neo-expressed in over 50% of cases in some cancer subtypes and associated with more dismal prognosis. The immunosuppressive effects of HLA-G may result in resistance to current immunotherapy drugs. The GEIA study explores the impact of HLA-G tumor expression on the efficacy of cancer immunotherapy in solid cancer patients.

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: September 10, 2020

Arms, Groups and Cohorts

  • Patients with advanced solid cancer treated with anti-PD(L)1
    • Adult patients with advanced solid cancer treated with anti-PD(L)1 immunotherapy with or without anti-CTLA4 immunotherapy.

Clinical Trial Outcome Measures

Primary Measures

  • Objective tumor response rate
    • Time Frame: at 6 months
    • The impact of HLA-G tumor expression (evaluated by immunohistochemistry) on tumor response rates (evaluated with iRECIST) in solid cancer patients treated with anti-PD(L)1 immunotherapy with or without anti-CTLA4 immunotherapy.

Secondary Measures

  • Progression free-survival
    • Time Frame: at 6 months
  • Progression free-survival
    • Time Frame: at 1 year
  • Progression free-survival
    • Time Frame: at 2 years
  • Overall survival
    • Time Frame: at 6 months
  • Overall survival
    • Time Frame: at 1 year
  • Overall survival
    • Time Frame: at 2 years
  • Specific disease survival
    • Time Frame: at 6 months
  • Specific disease survival
    • Time Frame: at 1 year
  • Specific disease survival
    • Time Frame: at 2 years
  • Incidence of adverse events
    • Time Frame: at 2 years
    • Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0
  • Soluble HLA-G levels counts
    • Time Frame: Up to 24 months
    • Soluble HLA-G levels will be evaluated by ELISA.The correlation between tumor HLA-G expression and soluble HLA-G levels will be studied.

Participating in This Clinical Trial

Inclusion Criteria

  • Age 18 or older – Social insurance – Ability to provide signed consent – Histologically proven solid cancer (non-small cell lung cancer, urothelial carcinoma, renal cell carcinoma, other) – Advanced and/or metastatic disease not accessible to local treatment – At least one target lesion according to iRECIST – Available fixed tumor sample for immunohistochemistry studies – Treatment with anti-PD(L)1 immunotherapy with or without anti-CTLA4 immunotherapy Exclusion Criteria:

  • Women pregnant or breastfeeding – Inability to consent to this research – Previous cancer immunotherapy (except BCG instillations for non-muscle infiltrative bladder cancer) – Patients chronically infected with HIV, HBV or HCV

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Stephane Culine, Pr, 01.42.49.42.47, stephane.culine@aphp.fr

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