Trial Title:
CD8 PET Imaging in Metastatic Solid Tumours
NCT ID:
NCT06534190
Condition:
Locally Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Nivolumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
89Zr-Df-crefmirlimab PET scan
Description:
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.
Arm group label:
CD8 PET imaging
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Immunotherapy treatment with Nivolumab
Arm group label:
CD8 PET imaging
Intervention type:
Drug
Intervention name:
Cetrelimab
Description:
Immunotherapy treatment with cetrelimab
Arm group label:
CD8 PET imaging
Intervention type:
Other
Intervention name:
zirconium Zr 89 crefmirlimab berdoxam
Description:
89Zr-Df-crefmirlimab will be administered followed by a PET scan 24 hours later
Arm group label:
CD8 PET imaging
Other name:
Zr-89 crefmirlimab berdoxam
Other name:
89Zr-Df-crefmirlimab
Other name:
89Zr-Df-IAB22M2C
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.
Criteria for eligibility:
Criteria:
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 principal investigator,
based on available clinical data, may benefit from anti-PD1 antibody therapy.
3. Disease progression following first-line therapy or any subsequent treatment line or
no superior standard line of therapy available.
4. At least 1 lesion that is accessible per investigator's assessment and eligible for
biopsy according to standard clinical care procedures.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Life expectancy ≥ 12 weeks.
8. Adequate organ and bone marrow function as defined below:
1. Hemoglobin ≥9.0 g/dL
2. Absolute neutrophil count ≥1.0 x 109/L
3. Absolute lymphocyte count ≥0.75 x 109/L
4. Platelet count ≥75 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 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.
ii. Aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN if liver tumour
involvement) iii. Alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver
tumour involvement) iv. Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5 x ULN if liver or
bone tumour involvement)
9. Signed informed consent.
10. Willingness and ability to comply with all protocol required procedures.
11. 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)).
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-Df-crefmirlimab infusion and nivolumab or cetrelimab treatment.
2. 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.
3. Prior ICI treatment, including but not limited to anti-PD1, anti-PD-L1 and
anti-CTLA4 therapeutic antibodies.
4. 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.
5. 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.
6. 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.
7. Prior allogeneic bone marrow transplantation or solid organ transplant.
8. 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.
9. Receipt of a live vaccine (including attenuated) within 30 days of planned start of
study medication.
10. Evidence of an active infection that requires systemic antibiotics within 2 weeks
prior to 89Zr-Df-crefmirlimab infusion.
11. At least 2 weeks recovered from COVID 19 infection, where this infection has to be
documented in the case record form.
12. 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.
13. Altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.
14. Sponsor employee/member of the clinical site study team and/or his or her immediate
family
15. Women with a positive serum chorionic gonadotropin HCG pregnancy test at the
screening/baseline visit. Breastfeeding women are also excluded.
16. 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:
- 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
- intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
- bilateral tubal ligation
- 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)
- and/or sexual abstinence.
17. Contraindications for MRI scan
18. Patients who have any splenic disorders, or had splenectomy, that could compromise
protocol objectives
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
VUMC
Address:
City:
Amsterdam
Zip:
1081 HV
Country:
Netherlands
Contact:
Last name:
C. W. Menke-van der Houven van Oordt, MD, PhD
Investigator:
Last name:
C. W. Menke-van der Houven van Oordt, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University Medical Center Groningen
Address:
City:
Groningen
Zip:
9713 GZ
Country:
Netherlands
Contact:
Last name:
Elisabeth G.E. de Vries, MD, PhD
Phone:
+31 50 361 2934
Email:
e.g.e.de.vries@umcg.nl
Contact backup:
Last name:
Daan G. Knapen, MD
Phone:
+31 50 361 6161
Email:
d.g.knapen@umcg.nl
Investigator:
Last name:
Elisabeth G.E. de Vries, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Daan G. Knapen, MD
Email:
Sub-Investigator
Facility:
Name:
Vall d'Hebron Institute of Oncology (VHIO) / Vall d'Hebron Institute Research (VHIR)
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Contact:
Last name:
E. G. Garralda, MD, PhD
Investigator:
Last name:
E. G. Garralda, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University of Cambridge
Address:
City:
Cambridge
Zip:
CB2 1TN
Country:
United Kingdom
Contact:
Last name:
B. Basu, MD, PhD
Investigator:
Last name:
B. Basu, MD, PhD
Email:
Principal Investigator
Start date:
August 2024
Completion date:
November 2028
Lead sponsor:
Agency:
University Medical Center Groningen
Agency class:
Other
Source:
University Medical Center Groningen
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06534190
