Non-small cell lung cancer
Conditions
Interventions
Trade Name: Nivolumab BMS
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
Other descriptive name: NIVOLUMAB
Concentration unit: mg/kg
Sponsors
VU Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
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 outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess uptake of 18F-PD-L1 and 89Zr- nivolumab in tumor lesions.;Secondary Objective: 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.;Primary end point(s): Visual and quantitative 18F-anti-PD-L1 and 89Zr-nivolumab uptake measurements in tumor (both tracers) and target irAE tissues (89Zr-nivolumab) and its correlation with blood and tissue immune parameters. ;Timepoint(s) of evaluation of this end point: Two years after start nivolumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable.;Timepoint(s) of evaluation of this end point: Not applicable. | — |
Countries
Netherlands
Contacts
Public ContactJoop de Langen
VU Medical Centre
Outcome results
None listed