Cancer metastases
Conditions
Interventions
Part A will serve to find the optimal tracer dose and the optimal interval
between tracer injection and PET scanning. Approximately 4 cohorts of about 2-3
patients each will undergo 89Zr-DFO-REGN376
additional patients may be enrolled
at that dose level if considered necessary to collect additional imaging and/or
safety data prior to starting part B. After completion of imaging, patients
will
the first
89Zr-DFO-REGN3767 PET scan will be performed at baseline, before starting
therapy. The second 89Zr-DFO-REGN3767 PET scan will be performed early in cycle
2 (within 7 days after administra
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 investigator, based on available clinical data, may benefit from PD1 antibody with or without platinum-based chemotherapy. 3. At least 1 lesion that is accessible per investigator*s assessment and eligible for biopsy according to standard clinical care procedures. 4. 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. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life expectancy >= 12 weeks. 7. Adequate organ and bone marrow function as defined below: a. Hemoglobin >=9.0 g/dL b. Absolute neutrophil count >=1.5 x 109/L c. Absolute lymphocyte count >=0.75 x 109/L d. Platelet count >=100 x 109/L e. Serum creatinine 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
Exclusion criteria
Exclusion criteria: 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-DFO-REGN3767 injection. 2. Prior ICI treatment, including but not limited to anti-PD1 and anti-PD-L1 therapeutic antibodies in the past 12 months or >= 12 months ago, in case the ICI treatment was terminated for progressive disease or toxicity. 3. Encephalitis, meningitis, or uncontrolled seizures in the year prior inclusion. 4. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy) 5. 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. 6. Documented allergic or acute hypersensitivity reaction attributed to antibody treatments 7. Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-DFO-REGN3767 injection or anticipation of need for a major surgical procedure during the course of the study. 8. For patients that will be treated with cemiplimab in combination with platinum containing chemotherapy, the following additional criteria apply: • Leucopenia <3 x 109/L • Estimated glomerular filtration rate < 60 mL/min/1.73 m2 • Cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), unstable angina, unstable cardiac arrhythmias, myocardial infarction < 3 months ago, or cerebrovascular accident < 6 months ago. • Hearing loss • Any other exclusion criteria, according to the local clinical practice guidelines for the chosen chemotherapy regimen. 9. 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. 10. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. • History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 11. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 4 weeks prior to 89Zr-DFO-REGN3767 injection. • 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 dis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Comparison of standardized uptake values in tumor lesions and tumor-to-blood ratios at different time points and different 89Zr-DFO-REGN3767 antibody dose levels. • To evaluate the biodistribution and PK of 89Zr-DFO-REGN3767 antibody by measuring standardized uptake value (SUV) on 89Zr-DFO-REGN3767 PET scans in patients with histologically or cytologically documented locally advanced or metastatic solid tumors who based on available clinical data may benefit from treatment with cemiplimab with or without platinum-based chemotherapy. • Safety evaluation through summaries of adverse events, changes in laboratory test results and changes in vital signs after exposure to 89Zr-DFO-REGN3767. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Comparison of tracer uptake, expressed as standardized uptake values, in different tumor lesions within and between patients on 89Zr-PET scans. • Correlation of tumor tracer uptake with tumor and immune cell LAG3 expression as assessed by immunohistochemistry on a tumor biopsy sample. • Correlation of tumor tracer uptake with response to cemiplimab with or without platinum-based chemotherapy, according to RECIST v1.1. • Assessment of change in tumor and normal organ tracer uptake after 2 cycles of cemiplimab with or without chemotherapy | — |
Countries
Netherlands
Outcome results
None listed