Phase Ib Study to Test the Feasibility and Safety of a Personalized Vaccine in Combination With Low-dose Cyclophosphamide in Patients With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)

This is a Phase Ib, single center study evaluating safety and feasibility of DC vaccine (autologous monocyte-derived dendritic cells [moDCs] pulsed with personalized peptides [PEP-DC]) given in combination with low dose cyclophosphamide, as SOC therapy in patients with advanced or recurrent metastatic NSCLC.

Patients with advanced or metastatic NSCLC (metastatic, recurrent and/or unresectable) who received standard of care therapy for advanced disease with no signs of progression will be eligible for this protocol. Patients may have received any number of prior treatments without restriction and any prior immunotherapy before enrollment to the study. However, only patients receiving the maintenance/continuation of SOC treatment options mentioned below are permitted to enter the study. Patients will be enrolled in the following two cohorts:

• Cohort 1: metastatic non-small cell lung cancer of any histology without any actionable oncogenic driver treated by SOC. Maintenance treatment with pemetrexed and/or maintenance/continuation of pembrolizumab, nivolumab or atezolizumab is allowed.
• Cohort 2: metastatic NSCLC with actionable oncogenic driver such as Epidermal Growth Factor Receptors (EGFR) mutation, ROS Proto-Oncogene 1 Receptor Tyrosine Kinase (ROS-1) or anaplastic lymphoma kinase (ALK) rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity.

In both cohorts, patients will receive six DC vaccinations Q3W (±3 days) in combination with low dose cyclophosphamide the day before vaccination. Each dose of vaccine (PEP-DC) will be formulated in two syringes of 525 microL each and administered on week 2 day 2 (W2D2) of each cycle, as subcutaneous injections. Patients will be vaccinated until vaccine exhaustion, disease progression, major toxicity or patient withdrawal, whichever is earlier. Additional DC vaccines may be administered Q3W (±3 days) if available until vaccine exhaustion or disease progression, whichever is earlier.