CD8 PET Imaging in Metastatic Solid Tumours
ConditionLocally Advanced Solid Tumor
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Medical Center Groningen
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
89Zr-Df-crefmirlimab PET scan
Radiation89Zr-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.
Nivolumab
DrugImmunotherapy treatment with Nivolumab
Cetrelimab
DrugImmunotherapy treatment with cetrelimab
zirconium Zr 89 crefmirlimab berdoxam
Other intervention89Zr-Df-crefmirlimab will be administered followed by a PET scan 24 hours later
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: CD8 PET imagingExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
2 years2
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.
Time frame
2 years3
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.
Time frame
2 years4
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.
Time frame
2 yearsSecondary outcomes
1
Incidence, nature, and severity of adverse events (AE) according to NCI-CTCAE v5.0
Adverse events will be assessed using the NCI-CTCAE v5.0 criteria, categorizing the severity from Grade 1 (mild) to Grade 5 (death).
Time frame
Up to 100 days after the last study procedure (treatment discontinuation visit)2
correlate mpMRI parameters
correlate mpMRI parameters such as Ktrans derived from DCE-MRI; f, D derived from IVIM-DWI and DDKI and K derived from DK-MRI with tumour and immune cell CD8 expression as well as T cell infiltration
Time frame
2 years3
Treatment response with nivolumab or cetrelimab
correlate response to treatment with nivolumab or cetrelimab, according to the RECIST v1.1 and iRECIST criteria with 89Zr-Df-crefmirlimab uptake in tumour lesions.
Time frame
2 yearsOther outcomes
1
89Zr-Df-crefmirlimab uptake with markers of immune infiltrates and other biomarkers for response to ICI therapy
Results of immunohistochemical (IHC) scoring of markers of immune infiltrate other then CD8 expression, such as PDL1, will be described as a semi-quantative score. 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.
Time frame
2 yearsSponsors and contacts
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Source ClinicalTrials.gov