clear cell renal cell carcinoma
Conditions
Interventions
Tumor nephrectomy at 7 weeks
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Adults at least 18 years of age • World Health Organization (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 will be based on clinical TNM and biopsy nuclear grade. These are: 1. cT1b-cT2a grade 4 cN0 cM0 2. cT2b grade 3-4 cN0 cM0 3. cT3 any grade cN0 cM0 4. 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 • Patient willing to undergo triple tumor biopsies and extra blood withdrawal during screening and in case of relapse • No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1, or LAG-3 • No immunosuppressive medications within 2 weeks prior start immunotherapy • Screening laboratory values must meet the following criteria: WBC >= 2.0x109/L, Neutrophils >=1.5x109/L, Platelets >=100 x109/L, Hemoglobin >=5.5 mmol/L, Creatinine
Exclusion criteria
Exclusion criteria: • Distantly metastasized RCC • Brain metastases (based on symptoms) • 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, except for subjects with vitiligo or resolved childhood asthma/atopy • Prior CTLA-4 or PD-1/PD-L1 or LAG-3 targeting immunotherapy • Radiotherapy prior or post-surgery • Patients will be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection; if treated and being at least one year free from HCV patients are allowed to participate • Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) • Allergies and Adverse Drug Reactions (like mastocytosis) • History of severe hypersensitivity reaction to any monoclonal antibody • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug(s) hazardous or obscure the interpretation of toxicity or adverse events; • 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 Relatlimab-specific exclusion criteria • Participants with history of myocarditis, regardless of etiology. • Troponin T (TnT) > 2 × institutional ULN. Participants with TnT levels between > 1 to 2 × ULN will be permitted if a repeat levels within 24 hours are 1 to 2 × ULN within 24 hours, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT repeat levels beyond 24 hours are
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of pathological responses following different neoadjuvant immunotherapy combinations in high-risk non-metastatic clear cell RCC in an adaptive trial design and the safety and feasibility of neoadjuvant IO approach in high-risk non-metastatic clear cell renal cell cancer patients | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives: 1. To describe the safety and feasibility of neoadjuvant IO approach in high-risk non- metastatic clear cell renal cell cancer patients 2. To investigate the objective response rate according to RECIST 1.1 3. To assess EFS, RFS, rate of metastasis and local recurrence rate at 5 years after start of treatment 4. To investigate surgical morbidity according to Clavien Dindo classification Exploratory objectives: Collection of peripheral blood and tissue collection (both fresh frozen and paraffin embedded) on pretreatment biopsies and post-treatment partial/total nephrectomies to correlate with pathological response rate and RFS for: 1. investigation of immune infiltrate and changes upon neoadjuvant immunotherapy by (multiplex) IHC/IF/ 2. investigation of predictive transcriptomics for response 3. investigation of TMB, frameshift mutations, INDELs, HERV-E 4. ctDNA (methylated DNA) to early predict response to treatment or progression 5. Collect fresh tumor materials for TIL isolation, TCR seq, sc RNA seq | — |
Countries
Netherlands
Outcome results
None listed