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

Not yet recruiting

• Conditions: Solid Tumor

• Registration Number: NCT04300088
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-03
• Study First Submitted: 2020-03-04
• Study First Submitted QC: 2020-03-06
• Last Update Submitted: 2020-03-06
• Study First Posted: 2020-03-09
• Last Update Posted: 2020-03-09
• Study Start: 2020-03-10
• Primary Completion: 2020-09-10
• Study Completion: 2025-09-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 281

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective tumor response rate	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 Outcome Measures

Name	Time	Method
Specific disease survival	at 2 years
Progression free-survival	at 2 years
Overall survival	at 2 years
Soluble HLA-G levels counts	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.
Incidence of adverse events	at 2 years	Adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0