To assess uptake of 18F-PD-L1 and 89Zr- nivolumab in tumor lesions.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess uptake of 18F-anti-PD-L1 and 89Zr-nivolumab in tumor lesions and in
normal tissue.
Secondary outcome
To assess the safety of 18F-anti-PD-L1 and 89Zr-nivolumab.
Characterize tumor uptake heterogeneity between patients and within and between
tumor lesions of the same patient.
Characterize the relationship between 18F-anti-PD-L1 and 89Zr- nivolumab tumor
uptake and tumor cell and tumor infiltrating lymphocyte (TIL) PD-1 and PD-L1
expression as well as other blood and tissue parameters (see section 6.3.16).
Explore the relationship between 89Zr- nivolumab and 18F-anti-PD-L1 organ
uptake with irAEs. The focus will be on the gut, lung, liver, thyroid and
pituitary.
Assess uptake of 18F-anti-PD-L1 and 89Zr- nivolumab in normal tissues to
evaluate the biodistribution and dosimetry.
Background summary
Tumor PD-L1+ immunohistochemistry (IHC) seems to be related to nivolumab
response, but the signal is not straightforward. Temporal and spatial variation
of tumor PD-L1 expression (within and between tumor lesions) might be
responsible for its suboptimal predictive value as biomarker of response.
Therefore there is a need to further validate tumor PD-L1 IHC as predictive
biomarker, as well as looking at alternatives. Biological imaging of PD-1 and
PD-L1 allows to monitor the PD-1/PD-L1 pathway from both sides, non-invasively.
Study objective
To assess uptake of 18F-PD-L1 and 89Zr- nivolumab in tumor lesions.
Study design
Single arm open label exploratory pilot (imaging) biomarker study.
To visualize the PD-1/PD-L1 pathway, positron emission tomography (PET) will be
combined with radiolabeled anti-PD-1 monoclonal antibody nivolumab
(89Zr-nivolumab) and with a radiolabeled PD-L1 binding biologic
(18F-anti-PD-L1), developed by BMS (18F-anti-PD-L1). Imaging with
89Zr-nivolumab allows for non-invasive quantification of its direct target, the
PD-1 receptor on tumor infiltrating lymphocytes, while imaging with
18F-anti-PD-L1 allows for non-invasive quantification of PD-L1 on tumor cells,
the most important (ex-vivo) tissue biomarker for patient selection in current
trials with anti-PD-(L)1 mAbs. Because the technique is non-invasive and whole
body, it allows for serial measurements of tumor uptake as well as looking at
heterogeneity within and between tumor lesions.
89Zr-nivolumab might also predict for immune related adverse events (irAE).
Whole body imaging with 89Zr-nivolumab allows to quantify nivolumab binding in
target irAE tissues and the level of tracer uptake might predict for irAEs.
Intervention
Not applicable.
Study burden and risks
Nivolumab is a highly active drug for the treatment of NSCLC in the second line
setting and beyond. It is therefore not unlikely that patients derive benefit
from this study. Toxicity is manageable and the safety profile acceptable. No
toxicity is expected from PET scans with tracer microdoses. The amount of
18F-anti-PD-L1 will be in the pico to nano molar quantity, far below the dosis
for a pharmacological effect. The amount of 89Z-nivolumab (1-2 mg) is far below
the nivolumab dose that is used in clinical studies and a pharmacological
effect is therefore not anticipated. The total amount of radiation exposure is
substantial, but immediate effects are not anticipated and because of the
limited life expectancy of patients with stage IV NSCLC the long term risk of
developing a secondary malignancy due to radiation exposure is only
theoretical. Up to two biopsies are allowed in this study. Although this is
demanding for patients, tumor biopsies in lung cancer patients are considered
safe with a low and manageable complication rate. No side effects are expected
from blood withdrawal.
De Boelelaan 1117
Amsterdam 1007 MB
NL
De Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Have a histologically or cytologically confirmed diagnosis of stage IV, EGFR WT and EML4-ALK fusion negative NCSLC and have received at least one line of platinum based doublet chemotherapy. EGFR and EML4-ALK testing is not necessary in patients with squamous NSCLC.
- Be willing and able to provide written informed consent/assent for the trial.
- Be > 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Must provide tissue from a histological biopsy of a tumor lesion that is not radiated prior to biopsy and obtained after the last line of systemic therapy to determine the actual PD-L1 status.
- Willing to undergo a second biopsy when the 18F-anti-PD-L1 or 89Zr-nivolumab PET scans show heterogeneous uptake.
- Have a performance status of 0-1 on the ECOG Performance Scale (Appendix 2).
- Demonstrate adequate organ function. All screening labs should be performed within 10 days of treatment initiation.
- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during the study and for 23 weeks after the last dose of nivolumab. Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception during the study and for 31 weeks after the last dose of nivolumab.
Exclusion criteria
A subject who meets any of the following criteria will be excluded from participation in this study:
- Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., * Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 0 or who has not recovered (i.e., * Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with asymptomatic CNS metastases are allowed to enter the study.
- Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids.
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject*s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B or C.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004760-11-NL |
| CCMO | NL55422.029.16 |