A phase II, open label, multi-center study of 89Zr-DF-Crefmirlimab for CD8 positron emission tomography in patients with locally advanced or metastatic solid tumours
- Conditions
- locally advanced or metastatic solid tumors10027656
- Registration Number
- NL-OMON56589
- Lead Sponsor
- niversitair Medisch Centrum Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 16
1. Age >= 18 years at the time of signing informed consent. 2. 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. 3. Disease progression following first-line therapy or any subsequent treatment line or no superior standard line of therapy available. 4. At least 1 lesion that is accessible per investigator*s assessment and eligible for biopsy according to standard clinical care procedures. 5. 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. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy >= 12 weeks. 8. Adequate organ and bone marrow function as defined below: a. Hemoglobin >=9.0 g/dL b. Absolute neutrophil count >=1.0 x 109/L c. Absolute lymphocyte count >=0.75 x 109/L d. Platelet count >=75 x 109/L e. Serum 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. Adequate hepatic function: i. Total 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. Aspartate aminotransferase (AST) <=2.5 x ULN (<=5 x ULN if liver tumour involvement) iii. Alanine aminotransferase (ALT) <=2.5 x ULN (<=5 x ULN if liver tumour involvement) iv. Alkaline phosphatase (ALP) <=2.5 x ULN (<=5 x ULN if liver or bone tumour involvement) 9. Signed informed consent. 10. Willingness and ability to comply with all protocol required procedures. 11. 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)).
1. 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.
2. 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.
3. Prior ICI treatment, including but not limited to anti-PD1, anti-PD-L1 and
anti-CTLA4 therapeutic antibodies.
4. 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.
5. 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.
• Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible for his study.
• Patients with controlled type I diabetes mellitus on a stable dose of insulin
regimen may be eligible for this study.
6. 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.
• Patients 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.
• The 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.
7. Prior allogeneic bone marrow transplantation or solid organ transplant.
8. Active infection with human immunodeficiency virus (HIV), hepatitis B,
hepatitis C or tuberculosis infection; or diagnosis of immunodeficiency.
• Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus
(HBV) at screening.
• Patients 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.
• Patients 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.
• Patients who are HCV antibody positive who have controlled infection
(undetectable HCV RNA by PCR
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Evaluation of the biodistribution and PK of 89Zr-Df-crefmirlimab antibody,<br /><br>through measuring standardized uptake value (SUV) on 89Zr-Df-crefmirlimab PET<br /><br>scans in patients with histologically or cytologically documented locally<br /><br>advanced or metastatic solid tumours. Correlation of tumour tracer uptake with<br /><br>tumour and immune cell CD8 expression, as assessed by immunohistochemistry.<br /><br>Changes in tumour volumetry, mpMRI parameters and MRI based texture metrics<br /><br>during immune checkpoint inhibitor treatment will also be measured. </p><br>
- Secondary Outcome Measures
Name Time Method <p>• Local and systemic signs and symptoms of infusion reactions, incidence of<br /><br>adverse events per NCI CTCAE v5.0 criteria, changes in laboratory test results,<br /><br>vital signs and 12-lead electrocardiogram (ECG) findings.<br /><br>• mpMRI parameters such as Ktrans derived from DCE-MRI; f, D derived from<br /><br>IVIM-DWI and DDKI and K derived from DK-MRI with tumour and immune cell CD8<br /><br>expression as well as T cell infiltration.<br /><br>• 89Zr-Df-crefmirlimab PET measurements (expressed as standardized uptake<br /><br>values) with radiologic response to treatment, according to (i)RECIST v1.1<br /><br>criteria.</p><br>