Prospective, randomized, neoadjuvant phase II study with combination immuno-oncology in primary clear cell renal cell cancer at risk for recurrence or distant metastases (NESCIO-trial)
Centra
NKI/Antoni van Leeuwenhoek ziekenhuis en Royal Free London NHS Foundation
Doel van het onderzoek
To investigate the efficacy and safety of different neoadjuvant immunotherapy combinations in high-risk non-metastatic clear cell RCC in an adaptive trial design
Behandeling:
Behandeling: neoadjuvant 2 cycles nivolumab 360mg versus 2 cycles nivolumab 3mg/kg + ipilimumab 1mg/kg versus 2 cycles nivolumab 360mg + relatlimab 360mg
Stadium:
intermediate to high-risk non-metastatic clear cell RCC
Belangrijkste in/exclusiecriteria:
- Patiënten met heldercellig nierkanker (niet uitgezaaid)
- 0Patiënten hebben nog geen eerdere behandeling met immuuntherapie of doelgerichte
- Inclusiecriteria:
- Adults at least 18 years of age
- WHO Performance Status 0 or 1
- Histologically confirmed resectable clear cell RCC (measurable according to RECIST 1.1), that can be biopsied, and no history of distant metastases
- Intermediate to high risk based on clinical TNM and biopsy nuclear grade. These are:
- 1. cT1b-cT2a grade 4 cN0 cM0
- 2. cT2b grade 3 cN0 cM0
- 3. cT3a grade 3-4 cN0 cM0
- 4. cT3b-cT4 any grade cN0 cM0
- 5. cT any cN1 (fully resectable) cM0
- No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years
- No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1, or LAG-3 or immunosuppressive medications within 6 months prior study inclusion
- Exclusiecriteria:
- Distantly metastasized RCC
- Non-clear cell RCC
- No measurable lesion according to RECIST 1.1
- Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications
- Prior CTLA-4 or PD-1/PD-L1 or LAG-3 targeting immunotherapy
- Radiotherapy prior or post-surgery
- Positive test for hepatitis B virus surface antigen or hepatitis C virus ribonucleic acid
- Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
- Allergies and Adverse Drug Reactions (like mastocytosis)
- History of severe hypersensitivity reaction to any monoclonal antibody
- Pregnant or nursing
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids
- Use of other investigational drugs before study drug administration 30 days and 5 half times before study inclusion
- Participants with history of myocarditis
- Troponin T (TnT) > 2 × institutional ULN.
- Left ventricular ejection fraction (LVEF) < 50% within 6 months prior to start of study treatment.
