Personalized DC Vaccines in Non Small Cell Lung Cancer
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Biological: Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine)
- Registration Number
- NCT05195619
- Lead Sponsor
- Centre Hospitalier Universitaire Vaudois
- Brief Summary
Phase Ib clinical trial using autologous dendritric cell (DC) vaccine loaded with personalized peptides (PEP) given in combination with low-dose cyclophosphamide, as standard of care (SOC) therapy in patients with advanced or recurrent metastatic NSCLC.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1 Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine) metastatic NSCLC 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 1 Low dose cyclophosphamide metastatic NSCLC 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 Autologous dendritic cell vaccine loaded with personalized peptides (PEP-DC vaccine) metastatic NSCLC with actionable oncogenic driver such as EGFR mutation, ROS-1 or ALK rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity. Cohort 2 Low dose cyclophosphamide metastatic NSCLC with actionable oncogenic driver such as EGFR mutation, ROS-1 or ALK rearrangement, currently receiving osimertinib, alectinib, lorlatinib, brigatinib or crizotinib as per SOC in each disease entity.
- Primary Outcome Measures
Name Time Method Number of patients who receive at least one dose of vaccine 3.5 years after study activation Feasibility will be evaluated by the number of patients who receive at least one dose of vaccine, among all enrolled patients.
Assessment of adverse events from informed consent form (ICF) signature until 30 days after last injection of DC vaccine/cyclophosphamide Safety will be assessed by recording all adverse events (AEs) observed from informed consent form (ICF) signature until 30 days after last injection of DC vaccine/cyclophosphamide.
Assessment of treatment-limiting toxicities 21 days (i.e. during the full vaccination period) Collection of events defined as related to vaccine administration. Patients showing any of them will be withdrawn from the study.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) up to 2 years from 1st vaccine injection Defined as the time from enrollment until death from any cause. Patients alive at the end of follow-up period will be censored at the last day the patient was known to be alive. OS survival rate will be estimated at 12 and 24 months after the date from first study treatment.
Overall response rate 1 (ORR1) From enrollment until 6 months Rate of patients with objective response (complete response or partial response) across all assessment time-points during the period from enrollment until 6 months.
Overall response rate 2 (ORR2) From enrollment to progression of the disease (ORR2) Rate of patients with objective response (complete response or partial response) across all assessment time-points during the period from enrollment to progression of the disease (ORR2).
Duration of response (DoR) up to 2 years from 1st vaccine injection Defined as the time from objective response (OR) until documented tumor progression date among responders.
Progression-free survival (PFS) up to 2 years from 1st vaccine injection Defined as the time from enrollment until documented tumor progression date (as defined by RECIST v1.1). For patients without progression or death (or patients that withdraw or are lost to follow-up), censoring will occur at the last tumor assessment. PFS rate will be estimated at 6, 12 and 24 months.
Trial Locations
- Locations (1)
CHUV Oncology Department
🇨🇭Lausanne, Vaud, Switzerland