Metastatic Solid Tumor
Conditions
Keywords
cancer, immune checkpoint inhibitor, positron emission tomography, LAG-3
Brief summary
This is an investigator-initiated, single-center, open-label clinical trial designed to evaluate the safety and PK of the PET tracer 89Zr-DFO-REGN3767 in patients prior to and during treatment.
Interventions
OTHER89Zr-DFO-REGN3767
Anti-LAG-3 PET imaging tracer
DRUGCemiplimab
Cemiplimab 350 mg every 3 weeks with or without platinum-based chemotherapy.
Sponsors
Regeneron Pharmaceuticals
University Medical Center Groningen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Hemoglobin ≥9.0 g/dL 2. Absolute neutrophil count ≥1.5 x 109/L 3. Absolute lymphocyte count ≥0.75 x 109/L 4. Platelet count ≥100 x 109/L 5. 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. 6. Adequate hepatic function: i. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumor 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 tumor involvement) iii. Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver tumor involvement) iv. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or bone tumor involvement) 8. Signed informed consent. 9. Willingness and ability to comply with all protocol required procedures.
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. 3. Encephalitis, meningitis or uncontrolled seizures in the year prior to 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: * Age \> 70 years * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optimal 89Zr-DFO-REGN3767 dose and PET imaging timepoint | 2 years | Determine the optimal 89Zr-DFO-REGN3767 dose and optimal PET imaging timepoint. |
| Pharmacokinetics (PK) of 89Zr-DFO-REGN3767 | 2 years | Description of PK of 89Zr-DFO-REGN3767 by measuring standardized uptake value (SUV) on PET scans performed 0, 2, 4 and/or 7 days after tracer injection. |
| Incidence of adverse events related to 89Zr-DFO-REGN3767 administration as assessed by CTCAE v5.0 | 2 years | Safety assessment through summaries of adverse events, changes in laboratory test results (if evaluation is indicated) and changes in vital signs. Adverse event data will be recorded and summarized according to NCI CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heterogeneity of 89Zr-DFO-REGN3767 antibody tumor uptake | 2 years | Heterogeneity of 89Zr-DFO-REGN3767 uptake will be evaluated by measuring standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the PET scan images. |
| Assessment of changes in tumor and normal organ uptake | 2 years | Patients enrolled in part B will undergo a PET scan at baseline and another one after 2 treatment cycles. 89Zr-DFO-REGN3767 tracer uptake will be quantified and expressed as standardized uptake value (SUV) in defined volumes of interest (VOIs) for both scans. The results of both PET scans will be compared to assess changes in imaging tracer uptake over time. |
| Correlation of tumor tracer uptake with tumor and immune cell LAG3 expression | 2 years | Results of immunohistochemical (IHC) scoring of immune cell LAG3 expression will be described as a semi-quantitative score using the percentage of positive cells (continuous variable), intensity and pattern of staining (discrete variable). These IHC results will be compared with imaging tracer standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the PET scan images. |
| Correlation of tumor tracer uptake with response to cemiplimab | 2 years | Response to therapy with cemiplimab (with or without chemotherapy) will be assessed according to the RECIST or iRECIST guidelines. These results will be compared with imaging tracer standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the PET scan images. |
Countries
Netherlands
Outcome results
None listed