ImmunoPET imaging with 89Zr-DFO-REGN3767 in patients with advanced solid cancer prior to and during treatment with cemiplimab with or without platinum-based chemotherapy

Recruiting

Conditions: Cancer
metastases
10027655

Registration Number: NL-OMON51900

Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 38

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 <=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 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 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• Comparison of standardized uptake values in tumor lesions and tumor-to-blood<br /><br>ratios at different time points and different 89Zr-DFO-REGN3767 antibody dose<br /><br>levels.<br /><br>• To evaluate the biodistribution and PK of 89Zr-DFO-REGN3767 antibody by<br /><br>measuring standardized uptake value (SUV) on 89Zr-DFO-REGN3767 PET scans in<br /><br>patients with histologically or cytologically documented locally advanced or<br /><br>metastatic solid tumors who based on available clinical data may benefit from<br /><br>treatment with cemiplimab with or without platinum-based chemotherapy.<br /><br>• Safety evaluation through summaries of adverse events, changes in laboratory<br /><br>test results and changes in vital signs after exposure to 89Zr-DFO-REGN3767.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Comparison of tracer uptake, expressed as standardized uptake values, in<br /><br>different tumor lesions within and between patients on 89Zr-PET scans.<br /><br>• Correlation of tumor tracer uptake with tumor and immune cell LAG3 expression<br /><br>as assessed by immunohistochemistry on a tumor biopsy sample.<br /><br>• Correlation of tumor tracer uptake with response to cemiplimab with or<br /><br>without platinum-based chemotherapy, according to RECIST v1.1.<br /><br>• Assessment of change in tumor and normal organ tracer uptake after 2 cycles<br /><br>of cemiplimab with or without chemotherapy</p><br>