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

Phase 1

• Conditions: Patients with metastatic solid tumors, where clinical data has shown a rationale for ICI therapy with or without platinum-based chemotherapy, will be included in this study.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004052-15-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-21
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
12.Pr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified