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

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Tumor

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with advanced solid cancer treated with anti-PD(L)1<br>Adult patients with advanced solid cancer treated with anti-PD(L)1 immunotherapy with or without anti-CTLA4 immunotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response rate | 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. | at 6 months | 

Secondary Outcome Measures

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