BLood Groups as Biomarker to Optimize Odds of Response to Anti-PD-1 Drugs

Study Overview
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Brief Summary
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BLOOD is an investigator-initiated, multicenter, prospective biomarker study in patients with advanced melanoma treated with anti-PD-1 monotherapy in the first-line setting. The studied products will be administered and managed within routine medical care in Belgium. The overall goal is (i) to investigate biomarkers for anti-PD-1 monotherapy and (ii) to gather evidence on real-life use of anti-PD-1 monotherapy in melanoma.

Official Title
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BLood Groups as Biomarker to Optimize Odds of Response to Anti-PD-1 Drugs (BLOOD Trial)

Conditions
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Melanoma, Cancer

Intervention / Treatment
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* Diagnostic Test: Blood sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven advanced melanoma. Anti-PD-1 monotherapy of advanced (unresectable or metastatic) melanoma (prescribed within its approved indication as per usual practice according to RIZIV/INAMI regulations) in the first-line setting. No prior systemic therapy for advanced melanoma. Have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. At least 18 years of age. Exclusion Criteria: Prior treatment with any drug specifically targeting T-cell co-stimulation or immune checkpoints (e.g., antibodies targeting PD-(L)1 or CTLA-4, chimeric antigen receptor T (CAR-T) cell therapy). Metastasis-directed therapy (surgery or radiotherapy) with definitive intent (local therapy to address symptomatic sites of disease is permitted). Previous systemic treatment for advanced melanoma. Active central nervous system (CNS) metastases (previously treated brain metastases are permitted if stable) or carcinomatous meningitis. Diagnosis of any other malignancy within 5 years prior to study inclusion, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low-risk prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease and symptoms.

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 melanoma<br>Patients receiving anti-PD-1 monotherapy (Nivolumab or Pembrolizumab) in the first-line setting | Diagnostic Test: Blood sample collection<br>* Whole venous blood of participants will be collected in EDTA tubes (max. 10 mL) at baseline, before start of first immunotherapy round. The Belgian Red Cross will perform serological blood group diagnostics, and molecular RBC typing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The association between ABO blood groups (specifically O vs A/B/AB) and anti-PD-1 monotherapy efficacy. | In terms of objective response rate (ORR) according to RECIST v1.1 | 25 weeks | 
| Descriptive data on real-life use of anti-PD-1 therapy. | Based on demographics (age, ethnicity, sex, height, weight (and Body Mass Index), smoking status, and gravida/para/abortus (if female)), melanoma history, clinical profile of participant at time of anti-PD-1 initiation, prior and/or concomitant intervention(s), duration of treatment exposure during the study, and effectiveness and safety of anti-PD-1 therapy. | 3, 6, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The association between ABO blood groups and anti-PD-1 monotherapy efficacy. | In terms of Overall Response Rate (ORR) / Disease Control Rate (DCR) / Best Overall Response (BOR) (RECIST v1.1) | 12, 25 weeks | 
| The association between ABO blood groups and anti-PD-1 monotherapy efficacy. | in terms of Progression-Free Survival (PFS) / Overall Survival (OS) (RECIST v1.1) | 3, 6, 12 months | 
| The association between Kell, Kidd, Duffy, MNS, Rhesus, and Dombrock blood group antigens and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between Kell, Kidd, Duffy, MNS, Rhesus, and Dombrock blood group antigens and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 
| The association between irregular antibodies and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between irregular antibodies and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 
| To evaluate the association between overall survival and other endpoints as defined in the primary endpoints. | (i.e., ORR, DCR, BOR, and PFS) | 12 months | 
| The association between steroid administration and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between steroid administration and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 
| The association between immunosuppressant administration and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between immunosuppressant administration and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 
| The association between antibiotics administration and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between antibiotics administration and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 
| The association between selected baseline and intermediate data (as listed in Outcome 2) and anti-PD-1 monotherapy efficacy. | In terms of ORR/DCR/BOR (RECIST v1.1) | 12, 25 weeks | 
| The association between selected baseline and intermediate data (as listed in Outcome 2) and anti-PD-1 monotherapy efficacy. | In terms of PFS/OS (RECIST v1.1) | 3, 6, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Anti-PD-1, Nivolumab, Pembrolizumab, Biomarker