CD8 PET Imaging in Metastatic Solid Tumours

NCT06534190 | Recruiting Phase 2 DMC

• 1 other identifier: 10353
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Locally Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Whole body distribution of 89Zr-Df-crefmirlimab

  Evaluate whole body distribution of 89Zr-Df-crefmirlimab in cancer patients prior to and during treatment with an anti-PD-1 antibody by measuring standardized uptake values (SUV) in tumours, healthy tissues and organs.

  2 years

• Pharmacokinetics (PK) of 89Zr-Df-crefmirlimab

  Description of pharmacokinetics (PK) of 89Zr-Df-crefmirlimab by measuring standardized uptake value (SUV) on PET scans performed in patients prior to and during treatment with an anti-PD-1 antibody.

  2 years

• Tumour tracer uptake with immune cell CD8 expression

  Results of immunohistochemical (IHC) scoring of CD8 expression will be described. 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.

  2 years

• Changes in tumour volumetry, mpMRI parameters and MRI based texture metrics

  DCE-MRI sequences will be evaluated and both semi-quantitative and pharmacokinetic quantitative parameters will be derived using a two-compartmental model.

  2 years

Secondary Outcomes (3)

• Incidence, nature, and severity of adverse events (AE) according to NCI-CTCAE v5.0

  Up to 100 days after the last study procedure (treatment discontinuation visit)

• correlate mpMRI parameters

  2 years

• Treatment response with nivolumab or cetrelimab

  2 years

Other Outcomes (1)

• 89Zr-Df-crefmirlimab uptake with markers of immune infiltrates and other biomarkers for response to ICI therapy

  2 years

Study Arms (1)

CD8 PET imaging

EXPERIMENTAL

89Zr-Df-crefmirlimab will be administered followed by a PET scan 24 hours later. All patients will undergo a 89Zr-Df-crefmirlimab PET scan at baseline and after treatment with the PD-1 antibody. All patients participating in this imaging trial will undergo preferably 2 but at least one tumour biopsy. The biopsy procedure(s) will be performed after the 89Zr-Df-crefmirlimab PET scan at baseline and/or after the 89Zr-Df-crefmirlimab PET on-treatment. After the first PET scan and tumour biopsy the patients will start treatment with PD-1 antibody nivolumab or cetrelimab.

Radiation: 89Zr-Df-crefmirlimab PET scan; Drug: Nivolumab; Drug: Cetrelimab; Other: zirconium Zr 89 crefmirlimab berdoxam

Interventions

Nivolumab DRUG

Immunotherapy treatment with Nivolumab

CD8 PET imaging

Cetrelimab DRUG

Immunotherapy treatment with cetrelimab

CD8 PET imaging

89Zr-Df-crefmirlimab PET scan RADIATION

89Zr-Df-crefmirlimab will be administered followed by a PET scan 24 hours later. All patients will undergo a 89Zr-Df-crefmirlimab PET scan at baseline and after treatment with the PD-1 antibody. All patients participating in this imaging trial will undergo preferably 2 but at least one tumour biopsy. The biopsy procedure(s) will be performed after the 89Zr-Df-crefmirlimab PET scan at baseline and/or after the 89Zr-Df-crefmirlimab PET on-treatment. After the first PET scan and tumour biopsy the patients will start treatment with PD-1 antibody nivolumab or cetrelimab.

CD8 PET imaging

zirconium Zr 89 crefmirlimab berdoxam OTHER

89Zr-Df-crefmirlimab will be administered followed by a PET scan 24 hours later

Also known as: Zr-89 crefmirlimab berdoxam, 89Zr-Df-crefmirlimab, 89Zr-Df-IAB22M2C

CD8 PET imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of signing informed consent.
• 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.
• Disease progression following first-line therapy or any subsequent treatment line or no superior standard line of therapy available.
• At least 1 lesion that is accessible per investigator's assessment and eligible for biopsy according to standard clinical care procedures.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count ≥1.0 x 109/L
• Absolute lymphocyte count ≥0.75 x 109/L
• Platelet count ≥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 hepatic function:
• i. Total bilirubin ≤1.5 x ULN (≤3 x ULN if liver tumour 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.

You may not qualify if:

• 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.
• 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 ICI treatment, including but not limited to anti-PD1, anti-PD-L1 and anti-CTLA4 therapeutic antibodies.
• 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.
• 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.
• 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.
• 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.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (4)

VUMC

Amsterdam, 1081 HV, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Vall d'Hebron Institute of Oncology (VHIO) / Vall d'Hebron Institute Research (VHIR)

Barcelona, 08035, Spain

NOT YET RECRUITING

University of Cambridge

Cambridge, CB2 1TN, United Kingdom

NOT YET RECRUITING

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Elisabeth G.E. de Vries, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisabeth GE de Vries, MD, PhD

CONTACT

+31 50 3612934; e.g.e.de.vries@umcg.nl

Daan G. Knapen, MD

CONTACT

+31 50 3616161; d.g.knapen@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: August 2, 2024
• Study Start: March 11, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: February 9, 2026

Record last verified: 2025-03

Locations

ES (1); NL (2); GB (1)