18F-PD-L1 PET/CT to predict response to nivolumab in patients with NSCLC

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 80

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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary outcome is progression-free survival of >=9 months .</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary outcomes include:<br /><br>- DCR after 3 months<br /><br>- PFS<br /><br>- progression-free survival (PFS) at 9 months<br /><br>- OS<br /><br>- correlation between PD-L1 expression measured by 18F-PD-L1 PET/CT-scan and<br /><br>PD-L1 expression measured by IHC.</p><br>