Lung cancer is the most commonly diagnosed cancer worldwide. Metastatic lung cancer is the
      leading cause of cancer mortality worldwide with a 5-year survival of less than 5%. With the
      approval of programmed cell death 1 (PD-1) inhibitors in advanced lung cancer, there has been
      an improvement in overall response rates and survival compared to chemotherapy.

      Checkpoint inhibition has become a primary treatment modality for vast number of cancers
      including lung cancer, prolonging survival in some patients. However, an important
      consideration is how to best select those patients who will respond to checkpoint inhibition.
      The biomarker that has been studied most extensively is PD-L1 expression. Studies have shown
      trends for increased response rates to PD-1 blockade in PD-L1 positive tumors.

      NSCLC patients are now approved for pembrolizumab monotherapy (PDL-1>50%) or for
      pembrolizumab in combination with chemotherapy (carboplatin/pemetrexed for non-squamous or
      carboplatin/paclitaxel) (no minimum PDL-1). As the ORR and PFS in both these trials indicate,
      however, there is a need for improvement in response rates and PFS in first-line treatments
      for patients with stage 4 NSCLC without genetically targetable alterations especially in
      those patients with PDL-1 <50%.

      There are both pre-clinical and clinical evidence supporting the combination of granulocyte
      macrophage colony stimulating factor (GM-CSF) with immunotherapy. GM-CSF is a hematopoietic
      growth factor that triggers proliferation and differentiation of hematopoietic progenitor
      cells, mainly neutrophils, monocytes/macrophages and myeloid-derived dendritic cells, and is
      approved by the FDA for this purpose.

      A phase II randomized clinical trial of unresectable stage III or IV melanoma patients
      comparing the effects of ipilimumab plus GM-CSF vs ipilimumab alone was shown to be both safe
      and had longer overall survival with lower toxicity than immunotherapy alone; 1 year survival
      for ipilimumab plus sargramostim was 68.9% (95% CI, 60.6%-85.5%) compared to 52.9% (95% CI,
      43.6%-62.2%) for ipilimumab alone.

      It is hypothesized that the use of GM-CSF along with a PD-1 inhibitor +/- pemetrexed is safe
      and will increase the overall response rate and progression-free survival in advanced NSCLC
      patients with PDL-1 of 1%-49%. This will establish the basis for further evaluation of
      GM-CSF+PD-1 in advanced NSCLC patients.