NIVOLUMAB for Metastatic solid tumours

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years at the time of signing informed consent."}
• {"criterion_text":"- Willingness and ability to comply with all protocol required procedures."}
• {"criterion_text":"- For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate (< 1% per year) when used consistently and correctly))."}
• {"criterion_text":"- Patients with histologically confirmed diagnosis of locally advanced or metastatic solid cancer types who, according to the opinion of the principal investigator, based on available clinical data, may benefit from anti-PD1 antibody therapy."}
• {"criterion_text":"- Disease progression following first-line therapy or any subsequent treatment line or no superior first line therapy available."}
• {"criterion_text":"- At least 1 lesion that is accessible per investigator’s assessment and eligible for biopsy according to standard clinical care procedures."}
• {"criterion_text":"- Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions except for lesions that have progressed after radiotherapy administered at least 3 months earlier."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1."}
• {"criterion_text":"- Life expectancy ≥ 12 weeks."}
• {"criterion_text":"- Adequate organ and bone marrow function as defined below: a.\tHemoglobin ≥9.0 g/dL b.\tAbsolute neutrophil count ≥1.0 x 109/L c.\tAbsolute lymphocyte count ≥0.75 x 109/L d.\tPlatelet count ≥75 x 109/L e.\tSerum creatinine ≤1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate > 30 mL/min/1.73 m2. A 24-hour urine creatinine collection may substitute for the calculated creatinine clearance to meet eligibility criteria. f.\tAdequate hepatic function: i.\tTotal bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumour involvement); Patients with Gilbert’s syndrome do not need to meet total bilirubin requirements, provided their total bilirubin is unchanged from their baseline. Gilbert’s syndrome must be documented appropriately as past medical history. ii.\tAspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumour involvement) iii.\tAlanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumour involvement) iv.\tAlkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumour involvement)"}
• {"criterion_text":"- Signed informed consent."}

Exclusion criteria

• {"criterion_text":"- Treatment with any approved anti-cancer therapy, investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to 89Zr-Df-crefmirlimab infusion and nivolumab or cetrelimab treatment."}
• {"criterion_text":"- Evidence of an active infection that requires systemic antibiotics within 2 weeks prior to 89Zr-Df-crefmirlimab infusion."}
• {"criterion_text":"- Evidence of an active COVID 19 infection. Thisinfection has to be documented in the case record form. When at least 2 weeks recovered from COVID 19, this is not an exclusion criterion anymore."}
• {"criterion_text":"- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of 89Zr-Df-crefmirlimab, or that may affect the interpretation of the results or render the patient at high risk from complications."}
• {"criterion_text":"- Altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent."}
• {"criterion_text":"- Sponsor employee/member of the clinical site study team and/or his or her immediate family"}
• {"criterion_text":"- Women with a positive serum chorionic gonadotropin HCG pregnancy test at the screening/baseline visit. Breastfeeding women are also excluded."}
• {"criterion_text":"- Women of childbearing potential* and sexually active men who are unwilling to practice highly effective contraception prior to the first dose of study therapy, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include: •\tstable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening •\tintrauterine device (IUD); intrauterine hormone-releasing system (IUS) •\tbilateral tubal ligation •\tvasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the women of childbearing potential (WOCBP) study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure) •\tand/or sexual abstinence."}
• {"criterion_text":"- Contraindications for MRI scan"}
• {"criterion_text":"- Patients who have any splenic disorders, or had splenectomy, that could compromise protocol objectives"}
• {"criterion_text":"- Symptomatic, untreated brain metastasis, leptomeningeal disease, or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and neurologically stable for at least 2 weeks prior to enrollment."}
• {"criterion_text":"- Prior ICI treatment, including but not limited to anti-PD1, anti-PD-L1 and anti-CTLA4 therapeutic antibodies."}
• {"criterion_text":"- Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-Df-crefmirlimab infusion or anticipation of need for a major surgical procedure during the course of the study."}
• {"criterion_text":"- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. •\tPatients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for his study. •\tPatients with controlled type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study."}
• {"criterion_text":"- Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor agents) within 4 weeks prior to 89Zr-Df-crefmirlimab infusion. •\tPatients who have received acute, low-dose, systemic immunosuppressant medications (e.g. a one-time of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the sponsor. •\tThe use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed."}
• {"criterion_text":"- Prior allogeneic bone marrow transplantation or solid organ transplant."}
• {"criterion_text":"- Active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or tuberculosis infection; or diagnosis of immunodeficiency. •\tPatients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening. •\tPatients with known HIV infection who have controlled infection (undetectable viral load (HIV ribonucleic acid (RNA) polymerase chain reaction (PCR)) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. •\tPatients with hepatitis B who have a controlled infection (serum HBV deoxyribonucleic acid (DNA) PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug. •\tPatients who are HCV antibody positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted. •\tPatients positive for HCV antibody are eligible only if PCR is negative for HCV RNA."}
• {"criterion_text":"- Receipt of a live vaccine (including attenuated) within 30 days of planned start of study medication."}

Primary endpoints

• {"endpoint_text":"- Evaluation of 89Zr-Df-crefmirlimab biodistribution in cancer patients on the PET images at baseline and during anti-PD-1 antibody therapy.","definition_or_measurement_approach":"Assessment by PET imaging at baseline and during anti-PD-1 antibody therapy to evaluate whole body distribution of 89Zr-Df-crefmirlimab."}
• {"endpoint_text":"- Assessment of the pharmacokinetic properties of 89Zr-Df-crefmirlimab in patients prior to and during treatment with an anti-PD-1 antibody","definition_or_measurement_approach":"Pharmacokinetic (PK) evaluation of 89Zr-Df-crefmirlimab pre-treatment and during anti-PD-1 therapy (sampling and PK analysis as per protocol)."}
• {"endpoint_text":"- Baseline and on-treatment 89Zr-Df-crefmirlimab uptake in tumours (expressed as standardized uptake value), CD8 expression in tumour biopsy samples, as determined by IHC.","definition_or_measurement_approach":"Tumour tracer uptake measured on PET expressed as standardized uptake value (SUV); CD8 expression assessed on tumour biopsy samples by immunohistochemistry (IHC)."}
• {"endpoint_text":"- Tumour volumetry, mpMRI parameters and MRI based texture metrics at baseline and during anti-PD-1 antibody therapy.","definition_or_measurement_approach":"Quantitative tumour volumetry and multiparametric MRI measures (mpMRI parameters and texture metrics) obtained at baseline and on-treatment for correlation with imaging and biomarker data."}

Secondary endpoints

• {"endpoint_text":"- Local and systemic signs and symptoms of infusion reactions, incidence of adverse events per NCI CTCAE v5.0 criteria, changes in laboratory test results, vital signs and 12-lead electrocardiogram (ECG) findings.","definition_or_measurement_approach":"Safety assessments including recording infusion reactions, adverse events graded by NCI CTCAE v5.0, laboratory changes, vital signs and 12-lead ECG findings."}
• {"endpoint_text":"- mpMRI parameters such as Ktrans derived from DCE-MRI; f, D derived from IVIM-DWI and DDKI and K derived from DK-MRI with tumour and immune cell CD8 expression as well as T cell infiltration.","definition_or_measurement_approach":"Correlation of specified mpMRI-derived parameters (Ktrans, IVIM-DWI metrics, DDKI/DK-MRI metrics) with tumour and immune cell CD8 expression and T-cell infiltration."}
• {"endpoint_text":"- 89Zr-Df-crefmirlimab PET measurements (expressed as standardized uptake values) with radiologic response to treatment, according to (i)RECIST v1.1 criteria.","definition_or_measurement_approach":"PET SUV measurements correlated with radiologic response according to RECIST v1.1 and iRECIST criteria."}

Netherlands

Earliest CTIS Part Ii Submission Date

13-11-2024

Latest Decision Or Authorization Date

22-09-2025

Processing Time Days

313

Number Of Sites

2

Number Of Participants

16

Spain

Earliest CTIS Part Ii Submission Date

16-02-2026

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

8

Number Of Sites

1

Number Of Participants

7

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands