TheranosticTrials.org

Clinical Trial · NCT06534190

CD8 PET Imaging in Metastatic Solid Tumours

Overview

This is a multi-center, single-arm trial designed to evaluate the safety and imaging characteristics of 89Zr-Df-crefmirlimab in patients with locally advanced or metastatic solid tumours prior to and during PD-1 antibody therapy.

Sponsor

University Medical Center Groningen

Phase

Phase 2

Contacts

Elisabeth GE de Vries, MD, PhD (CONTACT)

e.g.e.de.vries@umcg.nl

+31 50 3612934

Elisabeth G.E. de Vries, MD, PhD (PRINCIPAL_INVESTIGATOR)

Daan G. Knapen, MD (CONTACT)

d.g.knapen@umcg.nl

+31 50 3616161

ClinicalTrials.gov

NCT06534190

Drug / Compound

crefmirlimab

Isotope(s):
Target(s):
  • CD8 Cells
Ligand Class: Small Proteins and Antibody Fragments
Chelator: DFO

Eligibility

Inclusion

  • 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 administered at least 3 months earlier.
  • Patients with histologically confirmed diagnosis of locally advanced or metastatic solid cancer types who, according to the opinion of the principal investigator, based on available clinical data, may benefit from anti-PD1 antibody therapy.
  • Absolute lymphocyte count ≥0.75 x 109/L
  • 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.
  • Adequate organ and bone marrow function as defined below:
  • Willingness and ability to comply with all protocol required procedures.
  • Disease progression following first-line therapy or any subsequent treatment line or no superior standard line of therapy available.
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate (\< 1% per year) when used consistently and correctly)).
  • Absolute neutrophil count ≥1.0 x 109/L
  • At least 1 lesion that is accessible per investigator's assessment and eligible for biopsy according to standard clinical care procedures.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Platelet count ≥75 x 109/L
  • Life expectancy ≥ 12 weeks.
  • Hemoglobin ≥9.0 g/dL

Exclusion

  • 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.
  • bilateral tubal ligation
  • and/or sexual abstinence.
  • Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening.
  • vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the women of childbearing potential (WOCBP) study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure)
  • 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 have any splenic disorders, or had splenectomy, that could compromise protocol objectives
  • 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-Df-crefmirlimab, or that may affect the interpretation of the results or render the patient at high risk from complications.
  • Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • 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.
  • Major surgical procedure other than for diagnosis within 28 days prior to 89Zr-Df-crefmirlimab infusion or anticipation of need for a major surgical procedure during the course of the study.
  • Contraindications for MRI scan
  • 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.
  • stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening
  • Patients with controlled type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for his study.
  • 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.
  • Prior allogeneic bone marrow transplantation or solid organ transplant.
  • Receipt of a live vaccine (including attenuated) within 30 days of planned start of study medication.
  • 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. Highly effective contraceptive measures include:
  • intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
  • 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.
  • Women with a positive serum chorionic gonadotropin HCG pregnancy test at the screening/baseline visit. Breastfeeding women are also excluded.
  • Active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or tuberculosis infection; or diagnosis of immunodeficiency.
  • At least 2 weeks recovered from COVID 19 infection, where this infection has to be documented in the case record form.
  • Evidence of an active infection that requires systemic antibiotics within 2 weeks prior to 89Zr-Df-crefmirlimab infusion.
  • Prior ICI treatment, including but not limited to anti-PD1, anti-PD-L1 and anti-CTLA4 therapeutic antibodies.
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor agents) within 4 weeks prior to 89Zr-Df-crefmirlimab infusion.
  • Treatment with any approved anti-cancer therapy, investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to 89Zr-Df-crefmirlimab infusion and nivolumab or cetrelimab treatment.
  • 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.
  • Sponsor employee/member of the clinical site study team and/or his or her immediate family