Early stage (T1N0 and T2N0) non-small cell lung cancer
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive
Sponsors
VU Medical Centre
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: histologically histologically or cytologically confirmed diagnosis of early stage (T1bN0 and T2aN0) peripherally located NSCLC, eligible for surgical resection. Highly suspected NSCLC is defined as an a priori change of >85% that the lesion is malignant, according to the publication of Herder et al. (59) Be willing and able to provide written informed consent/assent for the trial. Be 18 years of age or older on day of signing imformed consent. Have measurable disease based on RECIST 1.1. Must provide tissue from a core or excisional biopsy of the primary tumor lesion. Have a performance status of 0-1 on the ECOG Performance Scale. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not ben free form menses for >1 year. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Is currently participating in or has participated in a study of an investigational agent or using investigational device within 4 weeks of the first dose of treatment. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days proor to the first dose of trial treatment. Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e. grade 1 or lower, or at baseling) 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 1 or who has not recovered (i.e. grade 1 or lower at baseline) from adverse events due to a previously administered agent. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cel carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented histroy of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. Has a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis. Has an active infection requiring systemic therapy. Has a histroy 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 bst interest of the subject to participate, in the opinion of the treating investigator. Has known psychiatric or substance abude disorders that would interfere with cooperation with the requirements of the trial. Is pregnant or breastfeedig, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Has known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA [qualitative] is detected). Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To identify the immunological response to combined SBRT and pembrolizumab treatment in early stage NSCLC. Expression rates and activation states of immune effector subsets will be assessed in tumor core biopsy specimens, peripheral blood and tumor draining lymph nodes (TDLNs) by means of EBUS derived fine needle aspirates. Samples will be taken before and after SBRT +/- pembrolizumab treatment and at surgery.;Secondary Objective: To assess the safety of combined SBRT and pembrolizumab treatment. To assess uptake (visual and quantitatively, expressed as SUVmax, SUVmean and SUVpeak) of radiolabeled pembrolizumab in the tumor and lymph nodes by use of PET. To evaluate radiation induces changes to healthy lung tissue after combined SBRT and pembrolizumab treatment in the resected lung lobe. ;Primary end point(s): Examination of tumor core biopsies and resection material. FACS analysis on EBUS-FNA of tumor draining lymphnodes (TDLNs) and peripheral blood to detect immunomodulation. ;Timepoint(s) of evaluation of this end point: 10 months after inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of clinical signs of radiation pneumonitis. The correlations of in-vivo PD-1 expression, quantified by immune-PET, with tissue and blood based immune-parameters. ;Timepoint(s) of evaluation of this end point: 10 months after inclusion | — |
Countries
Netherlands
Contacts
Public ContactSecretariaat Longziekten
VU Medical Centre
Outcome results
None listed