Non-small Cell Lung Cancer Clinical Trial
Official title:
89Zr-pembrolizumab-PET Imaging in Patients With Locally Advanced or Metastatic Melanoma or Non-small Cell Lung Cancer
This is a two center, single arm, investigator sponsored trial (IST) with the PET tracer 89Zr-pembrolizumab to evaluate in vivo whole body distribution of 89Zr-Pembrolizumab in a registered indication: locally advanced metastatic melanoma or non-small cell lung cancer before Pembrolizumab treatment.
Rationale: Immunotherapy targeting specific immune-regulatory checkpoints, mainly cytotoxic
T-lymphocyte antigen-4 (CTLA-4) and Programmed Death (PD1) or PD ligand 1 (PD-L1) have shown
spectacular effects in a broad range of solid malignancies, including melanoma and non-small
cell lung cancer (NSCLC). Pembrolizumab, is a monoclonal antibody that blocks the interaction
between PD-1 on T-cells with its ligands PD-L1 and PD-L2. Anti-tumor activity with an
acceptable side effect profile have been shown in melanoma and NSCLC.
Radio-labeling of pembrolizumab with the positron emission tomography (PET) radionuclide
89Zirkonium (89Zr) enables serial non-invasive imaging and quantification of distribution of
PD-1 in melanoma patients. By performing a 89Zr-pembrolizumab-PET scan prior to treatment
with pembrolizumab, the uptake of the tracer in the tumor lesions and normal organ
distribution can be evaluated, this could lead to new insights about heterogeneity of PD-1
expression, as well as the use of a 89Zr-pembrolizumab-PET as a complementary tool for
patient selection in the future.
Objective: Primary objective: To evaluate whole body distribution of 89Zr-pembrolizumab in
patients with locally advanced or metastatic melanoma or NSCLC. Secondary objectives: i) To
evaluate pharmacokinetics of 89Zr-pembrolizumab; ii) To assess the heterogeneity of
89Zr-pembrolizumab tumor uptake; iii) To describe safety of 89Zr-pembrolizumab; iv) To
correlate the tumor response of pembrolizumab, as measured by objective response rate (ORR)
according to standard RECIST v1.1 as assessed by the investigator, with specific tumor tracer
uptake.
Study design: This is a two center, single arm, investigator sponsored trail (IST) with the
PET tracer 89Zr-pembrolizumab to evaluate in vivo whole body distribution of
89Zr-pembrolizumab in a registered indication for locally advanced metastatic melanoma or
NSCLC before Pembrolizumab treatment.
Study population: Eligible are patients with locally advanced or metastatic melanoma or
NSCLC, who are eligible to receive Pembrolizumab treatment and who have at least one tumor
site that is accessible for a tumor biopsy.
Intervention : In part A of the imaging trial, a dose finding imaging study will be performed
to assess the optimal tracer protein dose of 89Zr-pembrolizumab and the optimal interval
between tracer injection and scanning. Approximately 3 cohorts of about 2-3 patients each
will undergo 89Zr-pembrolizumab-PET imaging before start of treatment with pembrolizumab. In
part B, 12 eligible patients will undergo 89Zr-pembrolizumab-PET imaging at baseline, with
the optimal tracer protein dose and scanning schedule as determined in part A. In total, a
maximum of 21 patients will be included.The purpose of part B of the study is to analyze the
whole body distribution and pharmacokinetics (PK) of 89Zr-Pembrolizumab. Tumor and normal
organ radioactive tracer uptake will be quantified as standardized uptake values (SUV). Tumor
biopsies will be collected at baseline and studied for various characteristics including
Programmed cell death-ligand 1 (PDL-1), PD-1 expression and tumor infiltrating lymphocytes.
Pembrolizumab treatment will be administered as standard of care Main study
parameters/endpoints: To evaluate whole body distribution of 89Zr-pembrolizumab in patients
with locally advanced or metastatic melanoma.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: For this imaging study patients have to make maximal 6 extra visits to the
clinic for screening, to receive tracer injection and for maximal 3 PET/CT scans and the
biopsy before start of standard treatment with pembrolizumab. The study ends after the last
imaging or biopsy (whichever comes first) and will approximately take 7 days. Whenever
possible, all procedures that are part of the study protocol will be planned during regular
visits to the hospital as part of care as usual.
89Zr-pembrolizumab-PET/CT implements a radiation burden of about 20 millisievert (mSv), and
1.5 mSv per low-dose CT scan. Besides PET imaging, patients will be asked to give in total 12
blood samples (85 mL), which will give minor discomfort. A metastases biopsy will be
performed, preferably from an easily accessible lesion to minimize the burden and risk for
the patient. Based on a literature review, the risk of tumor biopsies is considered low with
a small risk on significant/major complications or death. The risk associated with the
89Zr-pembrolizumab seems minor and although patients do not directly benefit from this study,
results of this study will be valuable for our understanding of the tumor immune response and
will guide further prospective research.
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