• To assess the relation between 18F-PD-L1 PET/CT outcome measures and progression-free survival of >=9 months according to RECIST 1.1.• To assess the relation between 18F-PD-L1 PET/CT outcome measures and patient outcome in terms of PFS and OS•…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is progression-free survival of >=9 months .
Secondary outcome
Secondary outcomes include:
- DCR after 3 months
- PFS
- progression-free survival (PFS) at 9 months
- OS
- correlation between PD-L1 expression measured by 18F-PD-L1 PET/CT-scan and
PD-L1 expression measured by IHC.
Background summary
PD-L1 immunohistochemistry (IHC) has only moderate predictive value for
response to PD-(L)1 gerichte immunotherapy in non-small cell lung cancer
(NSCLC). Heterogeneity of PD-L1 expression has been shown to be abundant within
tumors and between tumor lesions of the same patient. This questions whether a
small biopsy represents the true tumor PD-L1 status and might explain the
moderate and inconsistent predictive value of PD-L1 IHC using small biopsies.
Whole body 18F-PD-L1 PET/CT is a non-invasive technique that reflects the total
tumor PD-L1 expression status and includes information on target heterogeneity
within and between tumor lesions of the same patient.
Recently we showed in the CA209-408 study that PET imaging with 18F-PD-L1 is
safe and feasible, with good tumor-to-normal tissue contrast. 18F-PD-L1 uptake
correlated with PD-L1 IHC and, on average, patients with a partial response
demonstrated higher 18F-PD-L1 uptake than those with stable disease or
progressive disease.
We hypothesize that 18F-PD-L1 PET/CT might be a better predictor of durable
response to nivolumab (combination) treatment than PD-L1 IHC and that 18F-PD-L1
PET/CT could serve as a future biomarker for response prediction in the
clinical setting and future IO studies.
Study objective
• To assess the relation between 18F-PD-L1 PET/CT outcome measures and
progression-free survival of >=9 months according to RECIST 1.1.
• To assess the relation between 18F-PD-L1 PET/CT outcome measures and patient
outcome in terms of PFS and OS
• To assess the relation between 18F-PD-L1 PET/CT outcome measures and tumor
and stromal PD-L1 IHC.
• To assess the relation between 18F-PD-L1 PET/CT outcome measures and tumor
mutational burden (TMB).
• To assess the relation between 18F-PD-L1 PET/CT outcome measures and PBMC
based markers.
• To assess the correlation between complex biomarkers (combination of above
mentioned biomarkers) and patient outcome in terms of PFS and OS.
• To assess heterogeneity of 18F-anti-PD-L1 uptake between tumor lesions of the
same patient and the relation between these measures and (mixed) response.
• To obtain sufficient imaging data with the 18F-BMS-986229 tracer for
technical validation (imaging data obtained in this protocol will be combined
with the data obtained in the CA209-592 study).
Study design
This is a multicenter single arm biomarker exploration study. Eighty patients
with NSCLC that are eligible for first line chemo-immunotherapy, first line
nivolumab + ipilimumab or 2nd line and beyond immunotherapy monotherapy
nivolumab treatment will be enrolled in this trial. All subjects will undergo
one of two whole body 18F-PD-L1 PET/CT scan(s) within 10 days before start of
treatment. Patients will continue treatment according to label until disease
progression, withdrawal of patient consent or unacceptable toxicity.
Intervention
All subjects will undergo one or two whole body 18F-PD-L1 PET/CT scan(s) before
start of treatment. Patients will continue treatment according to label until
disease progression, withdrawal of patient consent or unacceptable toxicity.
Study burden and risks
The burden and risks associated with participation are considered low. Use of
positron emitting radionuclides means exposure to ionizing radiation. The
radiation exposure will be 4.5 mSv in total for each patient in case a recent
18F-FDG PET/CT scan is available and 9 mSv in case a new 18F-FDG PET/CT scan
has to be made. For the six patients who will receive two baseline 18F-PD-L1
PET/CT scans, 4,8 to 5,4mSv will be added to the total amount of radiation
burden. The long term risk of developing a secondary malignancy due to
radiation exposure is theoretical, because of the limited life expectancy of
patients with stage IV NSCLC and the low radiation burden. It is not expected
that patients will derive benefit from the PET scan results.
Since there is a lack of a well performing predictive biomarker of response,
the results of this imaging biomarker study can be of high interest for NSCLC
patients that are eligible for treatment with checkpoint inhibitors in the
future. Blood withdrawal is considered as a safe procedure.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
1. Have a histologically or cytologically confirmed diagnosis of stage IV, EGFR
WT and EML4-ALK fusion negative NSCLC. Mutational testing is not necessary in
patients with squamous NSCLC.
2. Eligible for first line chemo-immunotherapy, first line nivolumab +
ipilimumab or 2nd line and beyond PD-(L)1 immunotherapy monotherapy .
3. Be willing and able to provide written informed consent for the trial.
4. Be >= 18 years of age on day of signing informed consent.
5. Have measurable disease based on RECIST 1.1.
6. 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.
7. Have a performance status of 0-1 on the ECOG Performance Scale.
8. Demonstrate adequate hematologic and organ function, defined by the
following laboratory results. All screening laboratory tests should be
performed within 30 days prior to day 1 (PET imaging):
- Absolute neutrophil count (ANC) >= 1500 cells/µL
- WBC count >= 2000 cells/µL
- Platelet count >= 100.000/µL
- Hemoglobin >= 5.6 mmol/L
- AST and ALT <= 3 x ULN (<= 5 x ULN if liver metastases are present)
- Serum bilirubin <= 1.5 x ULN (except subjects with known Gilbert disease, who
can have total bilirubin < 3.0 mg/dL)
- Serum Creatinine <= 1.5 x ULN OR measured of calculated creatinine clearance
(GFR can also be used in place of creatinine or CrCl) >= 40 mL/min for subject
with creatinine levels > 1.5 x ULN.
Exclusion criteria
1. Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days prior to day 1 (PET imaging).
Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune
disease.
2. 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.
3. Has symptomatic central nervous system (CNS) metastases and/or carcinomatous
meningitis.
- Note: Subjects with asymptomatic CNS metastases are allowed to enter the
study.
- Note: Subjects with previously treated brain metastases may participate
provided they are clinically stable and not using steroids with > 10 mg daily
prednisone equivalent for at least 7 days prior to trial treatment.
4. 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.
5. Has evidence of interstitial lung disease or active, non-infectious
pneumonitis.
6. Has an active infection requiring systemic therapy.
7. 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.
8. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
9. 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.
10. 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 co-stimulation or immune checkpoint pathways.
11. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies).
12. 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 | EUCTR2017-005172-25-NL |
| CCMO | NL64568.031.18 |