| Eligibility |
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 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 disease,
mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
12. Prior allogeneic bone marrow transplantation or solid organ transplant.
13. 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 either spontaneously or in response to a successful
prior course of anti-HCV therapy) are permitted.
- Patients positive for HCV antibody are eligible only if PCR is negative for HCV
RNA.
14. Active infection, that requires systemic antibiotics within 2 weeks prior to
89Zr-DFO-REGN3767 injection.
15. 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-DFO-REGN3767, or that may affect the interpretation of
the results or render the patient at high risk from complications.
16. Receipt of a live vaccine (including attenuated) within 30 days of planned start of
study medication.
17. Altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.
18. Sponsor employee/member of the clinical site study team and/or his or her immediate
family
19. Women with a positive serum chorionic gonadotropin HCG pregnancy test at the
screening/baseline visit. Breastfeeding women are also excluded.
20. 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.
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