Anti PD-1 Neo-adjuvant Treatment for NSCLC
Condition: Non Small Cell Lung Carcinoma; Stage I; Stage II
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1

Summary: 
      A single arm, phase I, dose escalation trial and expansion cohort, examining the safety and
      feasibility of neoadjuvant pembrolizumab treatment for early resectable NSCLC patients.

      Hypothesis: The investigators hypothesize that response rate to neo-adjuvant pembrolizumab
      will be higher than the response rate of advanced NSCLC patients.
    

Detailed description: 
      16-28 patients with apparently operable NSCLC, clinically staged I-II with a resectable tumor
      would be recruited. Recruitment would be based on clinical assessment by a qualified Thoracic
      surgeon, with the appreciation that some of the recruited patients would eventually be deemed
      to be non-operable, or with a non-resectable disease, or to harbor a diagnosis different from
      NSCLC.

      Screen of consenting patients would include a diagnostic biopsy that includes core needle
      biopsy procedure. Fresh as well as formalin fixed paraffin embedded baseline tumor samples
      will be obtained according to common Standard Operating Procedures. Specimens would be
      processed as per pathology standard of care and two cores or more will be utilized later for
      the research study.

      A patient recruited after a previous diagnostic biopsy, would be eligible for the trial only
      if willing to undergo a repeat diagnostic procedure as above. Processing of biopsy material
      will be similar regardless if it is first or second biopsy.

      Trial treatment will commence only following pathological confirmation of NSCLC, complete
      staging including CT-PET and brain imaging, and positive pre-op cardiac and pulmonary
      assessment.

      Study schedule Dose levels of this study are defined by dose of drug as well as number of
      treatments and required interval from last treatment to surgery. At least 3 subjects in a
      dose cohort must complete the dose limiting toxicity (DLT) evaluation period before dosing is
      initiated at the next higher dose level. Only toxicities occurring during the DLT period will
      be considered as DLTs and utilized to inform dose escalation decisions. The DLT period starts
      with the first dose of pembrolizumab till 30 days post-surgery.

      Cohorts consists of 3-6 subjects per dose level, to be treated with study therapy following a
      3+3 schema.

      Dose escalation will proceed between cohorts according to a modified "3+3 design," as
      explained in the following scheme. Dose-limiting toxicity (DLT) is defined below and is
      confined in time as defined above. As a safety feature, a new dosing/schedule level will open
      only after the end of 30 post-operative days of the last patient in the previous cohort. If
      cohort one will be found to be too high as RP2D/schedule, the next patients will be treated
      at a dose/schedule level minus one. Only one step of dose reduction is planned.
    

Intervention name(s): Pembrolizumab 200 mg IV single dose; Pembrolizumab 200 mg IV twice interval 21 days; Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d; Pembrolizumab 100 mg I.V single dose; Surgical resection of tumor
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Pembrolizumab 200 mg IV single dose, 21 days later surgery; Pembrolizumab 200 mg IV twice interval 21 days, 21 days later surgery; Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d; Pembrolizumab 100 mg I.V single dose, surgery after 21 days.; Surgical resection of tumor by any of the acceptable procedures
Other intervention name(s): keytruda; keytruda; keytruda; keytruda; Lobectomy/pneumonectomy/bi-lobectomy
Intervention MeSH terms: Pembrolizumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment